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Sample records for antibody-dependent enhancement dengue

  1. Antibody-dependent enhancement of dengue virus infection is inhibited by SA-17, a doxorubicin derivative

    NARCIS (Netherlands)

    Ayala Nunez, Vanesa; Jarupathirun, Patsaporn; Kaptein, Suzanne; Neyts, Johan; Smit, Jolanda

    2013-01-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus (DENV)-induced disease during a heterologous re-infection. Despite ADE's clinical impact, only a few antiviral compounds have been assessed for their anti-ADE activity. We reported earlier

  2. Molecular mechanisms of dengue virus infection : cell tropism, antibody-dependent enhancement, and cytokines

    NARCIS (Netherlands)

    Flipse, Jacobus

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease in humans. Although most infections occur in the (sub)tropical areas, recent outbreaks in Italy and Madeira indicate that the virus is spreading into Europe. Despite its relevance, no vaccine or medications are available against this virus.

  3. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Miao Wang

    2017-05-01

    Full Text Available Dengue virus (DENV co-circulates as four serotypes (DENV1-4. Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS. Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR, a process known as antibody dependent enhancement (ADE. Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2 and DENV-2 prM monoclonal antibody (prM mAb could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo, interferon-α and γ receptor-deficient mice (AG6 were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10 and alaninea minotransferase (ALT in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies might be a new choice to be considered to

  4. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection.

    Science.gov (United States)

    Wang, Miao; Yang, Fan; Huang, Dana; Huang, Yalan; Zhang, Xiaomin; Wang, Chao; Zhang, Shaohua; Zhang, Renli

    2017-01-01

    Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo , interferon-α and γ receptor-deficient mice (AG6) were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo , suggested that anti-idiotypic antibodies might be a new choice to be considered to treat

  5. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Directory of Open Access Journals (Sweden)

    Ashley L Fink

    2017-07-01

    Full Text Available Dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4. At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE by binding to viral antigens and then Fcγ receptors (FcγR on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  6. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Science.gov (United States)

    Fink, Ashley L; Williams, Katherine L; Harris, Eva; Alvine, Travis D; Henderson, Thomas; Schiltz, James; Nilles, Matthew L; Bradley, David S

    2017-07-01

    Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  7. Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection

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    Rekha Khandia

    2018-04-01

    Full Text Available Antibody-dependent enhancement (ADE is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It is a serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV and Zika virus (ZIKV. In vitro experimental evidences have indicated the preventive, as well as a pathogenicity-enhancing role, of preexisting DENV antibodies in ZIKV infections. ADE has been confirmed in DENV but not ZIKV infections. Principally, the Fc region of the anti-DENV antibody binds with the fragment crystallizable gamma receptor (FcγR, and subsequent C1q interactions and immune effector functions are responsible for the ADE. In contrast to normal DENV infections, with ADE in DENV infections, inhibition of STAT1 phosphorylation and a reduction in IRF-1 gene expression, NOS2 levels, and RIG-1 and MDA-5 expression levels occurs. FcγRIIA is the most permissive FcγR for DENV-ADE, and under hypoxic conditions, hypoxia-inducible factor-1 alpha transcriptionally enhances expression levels of FcγRIIA, which further enhances ADE. To produce therapeutic antibodies with broad reactivity to different DENV serotypes, as well as to ZIKV, bispecific antibodies, Fc region mutants, modified Fc regions, and anti-idiotypic antibodies may be engineered. An in-depth understanding of the immunological and molecular mechanisms of DENV-ADE of ZIKV pathogenicity will be useful for the design of common and safe therapeutics and prophylactics against both viral pathogens. The present review discusses the role of DENV antibodies in modulating DENV/ZIKV pathogenicity/infection and strategies to counter ADE to protect against Zika infection.

  8. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    International Nuclear Information System (INIS)

    Chotiwan, Nunya; Roehrig, John T.; Schlesinger, Jacob J.; Blair, Carol D.; Huang, Claire Y.-H.

    2014-01-01

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection

  9. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    Energy Technology Data Exchange (ETDEWEB)

    Chotiwan, Nunya; Roehrig, John T. [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Schlesinger, Jacob J. [Department of Medicine, University of Rochester, Rochester, NY 14642 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H., E-mail: yxh0@cdc.gov [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2014-05-15

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.

  10. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

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    Koji Ichiyama

    Full Text Available Curdlan sulfate (CRDS, a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV. CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion. The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  11. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection.

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    Milly M Choy

    2015-11-01

    Full Text Available The mosquito-borne dengue virus (DENV is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue.

  12. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

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    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  13. Pichia pastoris-Expressed Bivalent Virus-Like Particulate Vaccine Induces Domain III-Focused Bivalent Neutralizing Antibodies without Antibody-Dependent Enhancement in Vivo

    OpenAIRE

    Rahul Shukla; Ravi K. Rajpoot; Upasana Arora; Ankur Poddar; Sathyamangalam Swaminathan; Navin Khanna; Navin Khanna; Navin Khanna

    2018-01-01

    Dengue, a significant public health problem in several countries around the world, is caused by four different serotypes of mosquito-borne dengue viruses (DENV-1, -2, -3, and -4). Antibodies to any one DENV serotype which can protect against homotypic re-infection, do not offer heterotypic cross-protection. In fact, cross-reactive antibodies may augment heterotypic DENV infection through antibody-dependent enhancement (ADE). A recently launched live attenuated vaccine (LAV) for dengue, which ...

  14. Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells cultured in vitro.

    Science.gov (United States)

    Tóth, F D; Mosborg-Petersen, P; Kiss, J; Aboagye-Mathiesen, G; Zdravkovic, M; Hager, H; Aranyosi, J; Lampé, L; Ebbesen, P

    1994-06-01

    We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C'-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C'-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADE of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE seems to be more efficient in enhancing HIV-1 replication than C'-ADE. While FcR-ADE leads to increased internalization of HIV-1, C'-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE are reactive with the gp120 viral envelope antigen, whereas antibodies involved in C'-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADE and C'-ADE may contribute to the spread of HIV-1 from mother to the fetus.

  15. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  16. Enhancement of antibody-dependent cellular cytotoxicity of cetuximab by a chimeric protein encompassing interleukin-15.

    Science.gov (United States)

    Ochoa, Maria Carmen; Minute, Luna; López, Ascensión; Pérez-Ruiz, Elisabeth; Gomar, Celia; Vasquez, Marcos; Inoges, Susana; Etxeberria, Iñaki; Rodriguez, Inmaculada; Garasa, Saray; Mayer, Jan-Peter Andreas; Wirtz, Peter; Melero, Ignacio; Berraondo, Pedro

    2018-01-01

    Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8 + T cells. On cell cultures, Sushi-IL15-Apo increases NK cell proliferation and survival as well as spontaneous and antibody-mediated cytotoxicity. Scavenger receptor class B type I (SR-B1) is the receptor for ApoA-I and is expressed on the surface of tumor cells. SR-B1 can adsorb the chimeric protein on tumor cells and can transpresent IL-15 to NK and CD8 + T cells. A transient NK-humanized murine model was developed to test the increase of ADCC attained by the chimeric protein in vivo . The EGFR + human colon cancer cell line HT-29 was intraperitoneally inoculated in immune-deficient Rag2 -/- γc -/- mice that were reconstituted with freshly isolated PBMCs and treated with the anti-EGFR mAb cetuximab. The combination of the Sushi-IL15-Apo protein and cetuximab reduced the number of remaining tumor cells in the peritoneal cavity and delayed tumor engraftment in the peritoneum. Furthermore, Sushi-IL15-Apo increased the anti-tumor effect of a murine anti-EGFR mAb in Rag1 -/- mice bearing subcutaneous MC38 colon cancer transfected to express EGFR. Thus, Sushi-IL15-Apo is a potent tool to increase the number and the activation of NK cells to promote the ADCC activity of antibodies targeting tumor antigens.

  17. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  18. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  19. Pichia pastoris-Expressed Bivalent Virus-Like Particulate Vaccine Induces Domain III-Focused Bivalent Neutralizing Antibodies without Antibody-Dependent Enhancement in Vivo

    Directory of Open Access Journals (Sweden)

    Rahul Shukla

    2018-01-01

    Full Text Available Dengue, a significant public health problem in several countries around the world, is caused by four different serotypes of mosquito-borne dengue viruses (DENV-1, -2, -3, and -4. Antibodies to any one DENV serotype which can protect against homotypic re-infection, do not offer heterotypic cross-protection. In fact, cross-reactive antibodies may augment heterotypic DENV infection through antibody-dependent enhancement (ADE. A recently launched live attenuated vaccine (LAV for dengue, which consists of a mixture of four chimeric yellow-fever/dengue vaccine viruses, may be linked to the induction of disease-enhancing antibodies. This is likely related to viral interference among the replicating viral strains, resulting in an unbalanced immune response, as well as to the fact that the LAV encodes prM, a DENV protein documented to elicit ADE-mediating antibodies. This makes it imperative to explore the feasibility of alternate ADE risk-free vaccine candidates. Our quest for a non-replicating vaccine centered on the DENV envelope (E protein which mediates virus entry into the host cell and serves as an important target of the immune response. Serotype-specific neutralizing epitopes and the host receptor recognition function map to E domain III (EDIII. Recently, we found that Pichia pastoris-expressed DENV E protein, of all four serotypes, self-assembled into virus-like particles (VLPs in the absence of prM. Significantly, these VLPs displayed EDIII and elicited EDIII-focused DENV-neutralizing antibodies in mice. We now report the creation and characterization of a novel non-replicating recombinant particulate vaccine candidate, produced by co-expressing the E proteins of DENV-1 and DENV-2 in P. pastoris. The two E proteins co-assembled into bivalent mosaic VLPs (mVLPs designated as mE1E2bv VLPs. The mVLP, which preserved the serotype-specific antigenic integrity of its two component proteins, elicited predominantly EDIII-focused homotypic virus

  20. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Ocaratuzumab, an Fc-engineered antibody demonstrates enhanced antibody-dependent cell-mediated cytotoxicity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Cheney, Carolyn M; Stephens, Deborah M; Mo, Xiaokui; Rafiq, Sarwish; Butchar, Jonathan; Flynn, Joseph M; Jones, Jeffrey A; Maddocks, Kami; O'Reilly, Adrienne; Ramachandran, Abhijit; Tridandapani, Susheela; Muthusamy, Natarajan; Byrd, John C

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is common in both developed and developing nations where the need for inexpensive and convenient administration of therapy is apparent. Ocaratuzumab is a novel Fc-engineered humanized IgG1 anti-CD20 monoclonal antibody (mAb) designed for effective antibody-dependent cell-mediated cytotoxicity (ADCC) at very low concentrations that may facilitate sub-cutaneous (vs. intravenous) dosing. Here, we report ocaratuzumab's potency against CLL cells. In vitro assessment of ocaratuzumab's direct cytotoxicity (DC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and ADCC was performed on CLL cells. Ocaratuzumab induced DC, CDC, and ADCP similarly to rituximab or ofatumumab (anti-CD20 mAbs). However, ocaratuzumab showed an advantage in NK cell-mediated ADCC over these antibodies. In allogeneic ADCC, [E:T (effector:target) ratios = 25:1, 12:1, 6:1], ocaratuzumab (10 µg/mL) improved ADCC by ~3-fold compared with rituximab or ofatumumab (P<0.001 all tested E:T ratios). Notably, the superiority of ocaratuzumab-induced ADCC was observed at low concentrations (0.1-10 ug/ml; P<0.03; allogeneic assays). In extended allogeneic ADCC E:T titration, ocaratuzumab (0.1 µg/mL) demonstrated 19.4% more cytotoxicity than rituximab (E:T = 0.38:1; P = 0.0066) and 21.5% more cytotoxicity than ofatumumab (E:T = 1.5:1; P = 0.0015). In autologous ADCC, ocaratuzumab (10 µg/mL) demonstrated ~1.5-fold increase in cytotoxicity compared with rituximab or ofatumumab at all E:T ratios tested (E:Ts = 25:1,12:1,6:1; all P<0.001). Obinutuzumab, a glyco-engineered anti-CD20 mAb, showed no improvement in ADCC activity compared with ocaratuzumab. The enhanced ADCC of ocaratuzumab suggests that it may be effective at low concentrations. If supported by clinical investigation, this feature could potentially allow for subcutaneous dosing at low doses that could expand the potential of administering chemoimmunotherapy in developing

  2. Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with FcαRI (CD89) binding.

    Science.gov (United States)

    Borrok, M Jack; Luheshi, Nadia M; Beyaz, Nurten; Davies, Gareth C; Legg, James W; Wu, Herren; Dall'Acqua, William F; Tsui, Ping

    2015-01-01

    Fc effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) are crucial to the efficacy of many antibody therapeutics. In addition to IgG, antibodies of the IgA isotype can also promote cell killing through engagement of myeloid lineage cells via interactions between the IgA-Fc and FcαRI (CD89). Herein, we describe a unique, tandem IgG1/IgA2 antibody format in the context of a trastuzumab variable domain that exhibits enhanced ADCC and ADCP capabilities. The IgG1/IgA2 tandem Fc format retains IgG1 FcγR binding as well as FcRn-mediated serum persistence, yet is augmented with myeloid cell-mediated effector functions via FcαRI/IgA Fc interactions. In this work, we demonstrate anti-human epidermal growth factor receptor-2 antibodies with the unique tandem IgG1/IgA2 Fc can better recruit and engage cytotoxic polymorphonuclear (PMN) cells than either the parental IgG1 or IgA2. Pharmacokinetics of IgG1/IgA2 in BALB/c mice are similar to the parental IgG, and far surpass the poor serum persistence of IgA2. The IgG1/IgA2 format is expressed at similar levels and with similar thermal stability to IgG1, and can be purified via standard protein A chromatography. The tandem IgG1/IgA2 format could potentially augment IgG-based immunotherapeutics with enhanced PMN-mediated cytotoxicity while avoiding many of the problems associated with developing IgAs.

  3. Autoimmunity in dengue pathogenesis

    Directory of Open Access Journals (Sweden)

    Shu-Wen Wan

    2013-01-01

    Full Text Available Dengue is one of the most important vector-borne viral diseases. With climate change and the convenience of travel, dengue is spreading beyond its usual tropical and subtropical boundaries. Infection with dengue virus (DENV causes diseases ranging widely in severity, from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia, and hemorrhage are the major clinical manifestations associated with severe DENV infection, yet the mechanisms remain unclear. Besides the direct effects of the virus, immunopathogenesis is also involved in the development of dengue disease. Antibody-dependent enhancement increases the efficiency of virus infection and may suppress type I interferon-mediated antiviral responses. Aberrant activation of T cells and overproduction of soluble factors cause an increase in vascular permeability. DENV-induced autoantibodies against endothelial cells, platelets, and coagulatory molecules lead to their abnormal activation or dysfunction. Molecular mimicry between DENV proteins and host proteins may explain the cross-reactivity of DENV-induced autoantibodies. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development. For the development of a safe and effective dengue vaccine, the immunopathogenic complications of dengue disease need to be considered.

  4. Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

    Science.gov (United States)

    Gessner, Bradford D; Halsey, Neal

    2017-06-14

    A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Wakako Furuyama

    2016-12-01

    Full Text Available Antibody-dependent enhancement (ADE of Ebola virus (EBOV infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fcγ-receptor IIa (FcγRIIa-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs is required for ADE of EBOV infection. We found that deletion of the FcγRIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface FcγRIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection.

  6. Immunological low-dose radiation modulates the pediatric medulloblastoma antigens and enhances antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Das, Arabinda; McDonald, Daniel; Lowe, Stephen; Bredlau, Amy-Lee; Vanek, Kenneth; Patel, Sunil J; Cheshier, Samuel; Eskandari, Ramin

    2017-03-01

    Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341). Induction of MB cell death was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Production of reactive oxygen species (ROS) was measured by fluorescent probes. Changes in the expression of  human leukocyte antigen (HLA) molecules and caspase-3 activities during treatment were analyzed using Western blotting and caspase-3 assay. Western blot analysis demonstrated that LDXR upregulated the expression of HLA class I and HLA II molecules by more than 20% compared with control and high-dose (12 Gy) groups in vitro. Several of these HLA subtypes, such as MAGE C1, CD137, and ICAM-1, have demonstrated upregulation. In addition, LDXR increases ROS production in association with phosphorylation of NF-κB and cell surface expression of mAb target molecules (HER2 and VEGF). These data suggest that a combined LDXR and mAb therapy can create a synergistic effect in vitro. These results suggest that LDXR modulates HLA molecules, leading to alterations in T-cell/tumor-cell interaction and enhancement of T-cell-mediated MB cell death. Also, low-dose radiotherapy combined with monoclonal antibody therapy may one day augment the standard treatment for MB, but more investigation is needed to prove its utility as a new therapeutic combination for MB patients.

  7. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab.

    Science.gov (United States)

    Fujii, Rika; Friedman, Eitan R; Richards, Jacob; Tsang, Kwong Y; Heery, Christopher R; Schlom, Jeffrey; Hodge, James W

    2016-06-07

    Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8+ T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.

  8. Dengue

    Science.gov (United States)

    Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It ... the world. Outbreaks occur in the rainy season. Dengue is rare in the United States. Symptoms include ...

  9. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab

    OpenAIRE

    Fujii, Rika; Friedman, Eitan R.; Richards, Jacob; Tsang, Kwong Y.; Heery, Christopher R.; Schlom, Jeffrey; Hodge, James W.

    2016-01-01

    Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 ch...

  10. A novel reporter system for neutralizing and enhancing antibody assay against dengue virus.

    Science.gov (United States)

    Song, Ke-Yu; Zhao, Hui; Jiang, Zhen-You; Li, Xiao-Feng; Deng, Yong-Qiang; Jiang, Tao; Zhu, Shun-Ya; Shi, Pei-Yong; Zhang, Bo; Zhang, Fu-Chun; Qin, E-De; Qin, Cheng-Feng

    2014-02-18

    Dengue virus (DENV) still poses a global public health threat, and no vaccine or antiviral therapy is currently available. Antibody plays distinct roles in controlling DENV infections. Neutralizing antibody is protective against DENV infection, whereas sub-neutralizing concentration of antibody can increase DENV infection, termed antibody-dependent enhancement (ADE). Plaque-based assay represents the most widely accepted method measuring neutralizing or enhancing antibodies. In this study, a novel reporter virus-based system was developed for measuring neutralization and ADE activity. A stable Renilla luciferase reporter DENV (Luc-DENV) that can produce robust luciferase signals in BHK-21 and K562 cells were used to establish the assay and validated against traditional plaque-based assay. Luciferase value analysis using various known DENV-specific monoclonal antibodies showed good repeatability and a well linear correlation with conventional plaque-based assays. The newly developed assay was finally validated with clinical samples from infected animals and individuals. This reporter virus-based assay for neutralizing and enhancing antibody evaluation is rapid, lower cost, and high throughput, and will be helpful for laboratory detection and epidemiological investigation for DENV antibodies.

  11. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  12. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2010-12-01

    Full Text Available Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmitted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theories or hypotheses immuno-patogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus infection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide a decent home and healthy, drinking water supply and proper waste disposal.

  13. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

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    Cavazzoni Andrea

    2012-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

  14. Immunopathogenesis of Dengue Virus-Induced Redundant Cell Death: Apoptosis and Pyroptosis.

    Science.gov (United States)

    Suwanmanee, San; Luplertlop, Natthanej

    Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.

  15. Dengue

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    ... emerged as a worldwide problem only since the 1950s. Although dengue rarely occurs in the continental United ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  16. Mutation of neutralizing/antibody-dependent enhancing epitope on spike protein and 7b gene of feline infectious peritonitis virus: influences of viral replication in monocytes/macrophages and virulence in cats.

    Science.gov (United States)

    Takano, Tomomi; Tomiyama, Yoshika; Katoh, Yasuichiroh; Nakamura, Michiyo; Satoh, Ryoichi; Hohdatsu, Tsutomu

    2011-03-01

    We previously prepared neutralizing monoclonal antibody (MAb)-resistant (mar) mutant viruses using a laboratory strain feline infectious peritonitis virus (FIPV) 79-1146 (Kida et al., 1999). Mar mutant viruses are mutated several amino acids of the neutralizing epitope of Spike protein, compared with the parent strain, FIPV 79-1146. We clarified that MAb used to prepare mar mutant viruses also lost its activity to enhance homologous mar mutant viruses, strongly suggesting that neutralizing and antibody-dependent enhancing epitopes are present in the same region in the strain FIPV 79-1146. We also discovered that amino acid mutation in the neutralizing epitope reduced viral replication in monocytes/macrophages. We also demonstrated that the mutation or deletion of two nucleotides in 7b gene abrogate the virulence of strain FIPV 79-1146. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

    OpenAIRE

    George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

    2017-01-01

    Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

  18. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  19. Structure and Function of the Non-Structural Protein of Dengue Virus and its Applications in Antiviral Therapy.

    Science.gov (United States)

    Xie, Qian; Zhang, Bao; Yu, JianHai; Wu, Qinghua; Yang, Fangji; Cao, Hong; Zhao, Wei

    2017-01-01

    Dengue fever, a type of global and tropical infectious disease, and its prevention has become a challenging issue worldwide. Antibody-dependent enhancement effects and the virus pathogenic mechanism have not yet been fully elucidated, hindering the development of dengue fever prevention and suitable drug treatment. There is currently no specific prevention and therapy in clinical trials, however, in recent years, studies have focused on the pathogenesis and treatment of dengue. Research focusing on dengue virus nonstructural protein in special drugs for the prevention and control of dengue fever is a new progress leading to improved understanding regarding the prevention and control of dengue fever and suitable drugs for the treatment. The main challenges regarding the structure of dengue virus nonstructural protein and the drugs for antiviral therapy are summarized in this paper.

  20. Environmental influences on antibody-enhanced dengue disease outcomes.

    Science.gov (United States)

    Diniz, Daniel Guerreiro; Fôro, César Augusto Raiol; Turiel, Maíra C Pereira; Sosthenes, Marcia C K; Demachki, Sâmia; Gomes, Giovanni Freitas; Rego, Carla M Damasceno; Magalhães, Marina Cutrim; Pinho, Brunno Gomes; Ramos, Juliana Pastana; Casseb, Samir M Moraes; Brito, Maysa de Vasconcelos; da Silva, Eliana Vieira Pinto; Nunes, Marcio Roberto Teixeira; Diniz, José Antonio Picanço; Cunningham, Colm; Perry, Victor Hugh; Vasconcelos, Pedro F Costa; Diniz, Cristovam W Picanço

    2012-12-01

    Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE.

  1. Enhancing the Immunogenicity of a Tetravalent Dengue DNA Vaccine

    Science.gov (United States)

    2016-08-01

    season’s influenza vaccine. There is no overlap with the proposed project. Title: Serological survey for Zika virus and other vector-borne pathogen...studying human immunology and pathogenesis of dengue virus infection Time Commitments: 5% 0.6 calendar months Supporting Agency: Military Infectious...attenuated dengue virus vaccine (LAV), and (3) inactivated dengue virus vaccine. Dengue fever ranks among the top infectious diseases that afflict

  2. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.

    Science.gov (United States)

    de Silva, Aravinda M; Harris, Eva

    2018-06-01

    Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  3. Autophagic machinery activated by dengue virus enhances virus replication

    International Nuclear Information System (INIS)

    Lee, Y.-R.; Lei, H.-Y.; Liu, M.-T.; Wang, J.-R.; Chen, S.-H.; Jiang-Shieh, Y.-F.; Lin, Y.-S.; Yeh, T.-M.; Liu, C.-C.; Liu, H.-S.

    2008-01-01

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication

  4. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

    Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

    2013-11-01

    Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

  5. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response

    Science.gov (United States)

    Flipse, Jacky; Smit, Jolanda M.

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection. PMID:26065421

  6. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

    Directory of Open Access Journals (Sweden)

    Jacky Flipse

    Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

  7. Seroprevalence of dengue IgG antibodies in symptomatic and asymptomatic individuals three years after an outbreak in Zhejiang Province, China.

    Science.gov (United States)

    Luo, Shuying; Cui, Weihong; Li, Chan; Ling, Feng; Fu, Tao; Liu, Qiyong; Ren, Jiangping; Sun, Jimin

    2018-02-23

    Cross-reacting antibodies enhanced dengue infection in humans and antibody dependent enhancement (ADE) have been proposed as early mechanisms underlying DHF/DSS. However, the duration of dengue IgG antibodies in the body as well as factors associated with said duration remain unclear. Blood samples from 59 dengue symptomatic persons and 48 asymptomatic individuals were collected. Study participant demographic information (including age in 2009, gender, and place of residence) were also collected. Serum samples were tested for dengue specific IgG by Panbio dengue IgG indirect enzyme-linked immunosorbent assay (ELISA). Chi-square tests and logistic regression analysis of dengue IgG antibodies seroprevalence divided by gender, age groups, and symptomatic or asymptomatic infection were conducted using the Statistical Package for the Social Sciences. Overall, 70 (65.42%) blood samples were seropositive for dengue IgG antibodies with similar seroprevalences found when dividing by gender and different age groups. However, seroprevalence of dengue IgG antibodies in samples from dengue symptomatic persons was significantly higher than that in samples from asymptomatic individuals (96.61% vs 27.08%) according to multivariable logistic regression analysis, the odds ratio (OR) of the factor was 76.731. Dengue IgG antibodies were detectable in samples from most individuals three years after infection. Dengue symptomatic persons had a higher dengue IgG prevalence compared to asymptomatic individuals.

  8. Dengue envelope-based 'four-in-one' virus-like particles produced using Pichia pastoris induce enhancement-lacking, domain III-directed tetravalent neutralising antibodies in mice.

    Science.gov (United States)

    Rajpoot, Ravi Kant; Shukla, Rahul; Arora, Upasana; Swaminathan, Sathyamangalam; Khanna, Navin

    2018-06-05

    Dengue is a significant public health problem worldwide, caused by four antigenically distinct mosquito-borne dengue virus (DENV) serotypes. Antibodies to any given DENV serotype which can afford protection against that serotype tend to enhance infection by other DENV serotypes, by a phenomenon termed antibody-dependent enhancement (ADE). Antibodies to the viral pre-membrane (prM) protein have been implicated in ADE. We show that co-expression of the envelope protein of all four DENV serotypes, in the yeast Pichia pastoris, leads to their co-assembly, in the absence of prM, into tetravalent mosaic VLPs (T-mVLPs), which retain the serotype-specific antigenic integrity and immunogenicity of all four types of their monomeric precursors. Following a three-dose immunisation schedule, the T-mVLPs elicited EDIII-directed antibodies in mice which could neutralise all four DENV serotypes. Importantly, anti-T-mVLP antibodies did not augment sub-lethal DENV-2 infection of dengue-sensitive AG129 mice, based on multiple parameters. The 'four-in-one' tetravalent T-mVLPs possess multiple desirable features which may potentially contribute to safety (non-viral, prM-lacking and ADE potential-lacking), immunogenicity (induction of virus-neutralising antibodies), and low cost (single tetravalent immunogen produced using P. pastoris, an expression system known for its high productivity using simple inexpensive media). These results strongly warrant further exploration of this vaccine candidate.

  9. Demam Berdarah Dengue: Epidemiologi, Patogenesis, dan Faktor Risiko Penularan

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2013-02-01

    Full Text Available Abstract. Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmit­ted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theo ries or hypotheses immunopatogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus in­fection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide adecent home and healthy, drinking water supply and proper waste disposal.Keywords: dengue hemorrhagic fever (DHF, epidemiology of DHF, pathogenesis of DHF, transmission risk factors of DHF

  10. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

    Science.gov (United States)

    Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

    2017-10-01

    Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  12. Neutralization of antibody-enhanced dengue infection by VIS513, a pan serotype reactive monoclonal antibody targeting domain III of the dengue E protein

    Science.gov (United States)

    Robinson, Luke N.; Ong, Li Ching; Rowley, Kirk J.; Winnett, Alexander; Tan, Hwee Cheng; Hobbie, Sven; Shriver, Zachary; Babcock, Gregory J.; Alonso, Sylvie; Ooi, Eng Eong

    2018-01-01

    Dengue virus (DENV) infection imposes enormous health and economic burden worldwide with no approved treatment. Several small molecules, including lovastatin, celgosivir, balapiravir and chloroquine have been tested for potential anti-dengue activity in clinical trials; none of these have demonstrated a protective effect. Recently, based on identification and characterization of cross-serotype neutralizing antibodies, there is increasing attention on the potential for dengue immunotherapy. Here, we tested the ability of VIS513, an engineered cross-neutralizing humanized antibody targeting the DENV E protein domain III, to overcome antibody-enhanced infection and high but brief viremia, which are commonly encountered in dengue patients, in various in vitro and in vivo models. We observed that VIS513 efficiently neutralizes DENV at clinically relevant viral loads or in the presence of enhancing levels of DENV immune sera. Single therapeutic administration of VIS513 in mouse models of primary infection or lethal secondary antibody-enhanced infection, reduces DENV titers and protects from lethal infection. Finally, VIS513 administration does not readily lead to resistance, either in cell culture systems or in animal models of dengue infection. The findings suggest that rapid viral reduction during acute DENV infection with a monoclonal antibody is feasible. PMID:29425203

  13. Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity

    Science.gov (United States)

    Shen, Yang; Zeng, Lin; Zhu, Aiping; Blanc, Tim; Patel, Dipa; Pennello, Anthony; Bari, Amtul; Ng, Stanley; Persaud, Kris; Kang, Yun (Kenneth); Balderes, Paul; Surguladze, David; Hindi, Sagit; Zhou, Qinwei; Ludwig, Dale L.; Snavely, Marshall

    2013-01-01

    Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies. PMID:23567210

  14. Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

    Science.gov (United States)

    Halstead, Scott B

    2017-11-07

    During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dengue serotype immune-interactions and their consequences for vaccine impact predictions

    Directory of Open Access Journals (Sweden)

    José Lourenço

    2016-09-01

    Full Text Available Dengue is one of the most important and wide-spread viral infections affecting human populations. The last few decades have seen a dramatic increase in the global burden of dengue, with the virus now being endemic or near-endemic in over 100 countries world-wide. A recombinant tetravalent vaccine candidate (CYD-TDV has recently completed Phase III clinical efficacy trials in South East Asia and Latin America and has been licensed for use in several countries. The trial results showed moderate-to-high efficacies in protection against clinical symptoms and hospitalisation but with so far unknown effects on transmission and infections per se. Model-based predictions about the vaccine's short- or long-term impact on the burden of dengue are therefore subject to a considerable degree of uncertainty. Furthermore, different immune interactions between dengue's serotypes have frequently been evoked by modelling studies to underlie dengue's oscillatory dynamics in disease incidence and serotype prevalence. Here we show how model assumptions regarding immune interactions in the form of antibody-dependent enhancement, temporary cross-immunity and the number of infections required to develop full immunity can significantly affect the predicted outcome of a dengue vaccination campaign. Our results thus re-emphasise the important gap in our current knowledge concerning the effects of previous exposure on subsequent dengue infections and further suggest that intervention impact studies should be critically evaluated by their underlying assumptions about serotype immune-interactions.

  16. Enhancing the sensitivity of Dengue virus serotype detection by RT-PCR among infected children in India.

    Science.gov (United States)

    Ahamed, Syed Fazil; Vivek, Rosario; Kotabagi, Shalini; Nayak, Kaustuv; Chandele, Anmol; Kaja, Murali-Krishna; Shet, Anita

    2017-06-01

    Dengue surveillance relies on reverse transcription-polymerase chain reaction (RT-PCR), for confirmation of dengue virus (DENV) serotypes. We compared efficacies of published and modified primer sets targeting envelope (Env) and capsid-premembrane (C-prM) genes for detection of circulating DENV serotypes in southern India. Acute samples from children with clinically-diagnosed dengue were used for RT-PCR testing. All samples were also subjected to dengue serology (NS1 antigen and anti-dengue-IgM/IgG rapid immunochromatographic assay). Nested RT-PCR was performed on viral RNA using three methods targeting 654bp C-prM, 511bp C-prM and 641bp Env regions, respectively. RT-PCR-positive samples were validated by population sequencing. Among 171 children with suspected dengue, 121 were dengue serology-positive and 50 were dengue serology-negative. Among 121 serology-positives, RT-PCR detected 91 (75.2%) by CprM654, 72 (59.5%) by CprM511, and 74 (61.1%) by Env641. Among 50 serology-negatives, 10 (20.0%) were detected by CprM654, 12 (24.0%) by CprM511, and 11 (22.0%) by Env641. Overall detection rate using three methods sequentially was 82.6% (100/121) among serology-positive and 40.0% (20/50) among serology-negative samples; 6.6% (8/120) had co-infection with multiple DENV serotypes. We conclude that detection of acute dengue was enhanced by a modified RT-PCR method targeting the 654bp C-prM region, and further improved by using all three methods sequentially. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

    Science.gov (United States)

    Yamanaka, Atsushi; Konishi, Eiji

    2017-09-25

    Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

  18. Dengue Epidemiology

    Science.gov (United States)

    ... and dengue shock syndrome (DSS). Transmission of the Dengue Virus Dengue is transmitted between people by the ... the vectors is too infrequent to sustain transmission. Dengue is an Emerging Disease The four dengue viruses ...

  19. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    Directory of Open Access Journals (Sweden)

    Scott R Fry

    2011-06-01

    Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

  20. Flavone Enhances Dengue Virus Type-2 (NGC Strain Infectivity and Replication in Vero Cells

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    Keivan Zandi

    2012-02-01

    Full Text Available This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone on DENV-2 infectivity in Vero cells. Virus adsorption and attachment and intracellular virus replication were investigated using a foci forming unit assay (FFUA and quantitative RT-PCR, respectively. Addition of flavone (100 μg/mL significantly increased the number of DENV-2 foci by 35.66% ± 1.52 and 49.66% ± 2.51 when added during and after virus adsorption to the Vero cells, respectively. The average foci size after 4 days of infection increased by 33% ± 2.11 and 89% ± 2.13. The DENV-2 specific RNA copy number in the flavone-treated infected cells increased by 6.41- and 23.1-fold when compared to the mock-treated infected cells. Flavone (100 μg/mL did not promote or inhibit Vero cell proliferation. The CC50 value of flavone against Vero cells was 446 µg/mL. These results suggest that flavone might enhance dengue virus replication by acting antagonistically towards flavonoids known to inhibit dengue virus replication.

  1. Modeled Forecasts of Dengue Fever in San Juan, PR Using NASA Satellite Enhanced Weather Forecasts

    Science.gov (United States)

    Morin, Cory; Quattrochi, Dale; Zavodsky, Bradley; Case, Jonathan

    2015-01-01

    Dengue virus is transmitted between humans and mosquitoes of the genus Aedes and causes approximately 96 million cases of disease (dengue fever) each year (Bhatet al. 2013). Symptoms of dengue fever include fever, headache, nausea, vomiting, and eye, muscle and joint pain (CDC). More sever manifestations such as abdominal pain, bleeding from nose and gums, vomiting of blood, and clammy skin occur in rare cases of dengue hemorrhagic fever (CDC). Dengue fever occurs throughout tropical and sub-tropical regions worldwide, however, the geographical range and size of epidemics is increasing. Weather and climate are drivers of dengue virus transmission dynamics (Morin et al. 2013) by affecting mosquito proliferation and the virus extrinsic incubation period (i.e. required time for the virus to replicate and disseminate within the mosquito before it can retransmit the virus).

  2. Advances in the development of vaccines for dengue fever

    Directory of Open Access Journals (Sweden)

    Simmons M

    2012-05-01

    Full Text Available Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV serotypes 1–4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector control the only method of prevention. A particular challenge with DENV is that a successful vaccine has to be effective against all four serotypes without predisposing for antibody-mediated enhanced disease. In this review, we discuss the current lead vaccine candidates in clinical trials, as well as some second-generation vaccine candidates undergoing preclinical evaluation. In addition, we discuss DENV epidemiology, clinical disease and strategies used for Flavivirus antivirals in the past, the development of new DENV therapeutics, and their potential usefulness for prophylaxis and treatment.Keywords: tetravalent dengue vaccine, live attenuated vaccine, purified inactivated vaccine, DNA vaccine, antibody-dependent enhancement, antivirals

  3. Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

    Science.gov (United States)

    Thomas, Stephen J.; Aldstadt, Jared; Jarman, Richard G.; Buddhari, Darunee; Yoon, In-Kyu; Richardson, Jason H.; Ponlawat, Alongkot; Iamsirithaworn, Sopon; Scott, Thomas W.; Rothman, Alan L.; Gibbons, Robert V.; Lambrechts, Louis; Endy, Timothy P.

    2015-01-01

    Dengue is of public health importance in tropical and sub-tropical regions. Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized subjects with confirmed dengue (initiates) and associated cluster individuals (associates) with entomologic sampling. A total of 438 associates were enrolled from 208 houses with household members with a history of fever, located within a 200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory-confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected were dengue polymerase chain reaction positive (PCR+). There was a significant relationship between spatial proximity to the initiate case and likelihood of detecting DENV from associate cases and Aedes mosquitoes. The viral detection rate from human hosts and mosquito vectors in this study was higher than previously observed by the study team in the same geographic area using different methodologies. We propose that the sampling strategy used in this study could support surveillance of DENV transmission and vector interactions. PMID:25986580

  4. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.

    Science.gov (United States)

    Screaton, Gavin; Mongkolsapaya, Juthathip

    2017-07-17

    A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Dengue and Severe Dengue

    Science.gov (United States)

    ... all regions of WHO in recent years. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus . This mosquito also transmits chikungunya, yellow fever and Zika infection. Dengue is widespread throughout the tropics, with ...

  6. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

    Directory of Open Access Journals (Sweden)

    Denicar Lina Nascimento Fabris Maeda

    2017-09-01

    Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

  7. The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden

    Science.gov (United States)

    Boross, Peter; Jansen, J.H. Marco; de Haij, Simone; Beurskens, Frank J.; van der Poel, Cees E.; Bevaart, Lisette; Nederend, Maaike; Golay, Josée; van de Winkel, Jan G.J.; Parren, Paul W.H.I.; Leusen, Jeanette H.W.

    2011-01-01

    Background CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Design and Methods Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Results Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Conclusions Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms. PMID:21880632

  8. Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

    Science.gov (United States)

    Kurdi, Ahmed T; Glavey, Siobhan V; Bezman, Natalie A; Jhatakia, Amy; Guerriero, Jennifer L; Manier, Salomon; Moschetta, Michele; Mishima, Yuji; Roccaro, Aldo; Detappe, Alexandre; Liu, Chia-Jen; Sacco, Antonio; Huynh, Daisy; Tai, Yu-Tzu; Robbins, Michael D; Azzi, Jamil; Ghobrial, Irene M

    2018-04-13

    Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcγR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Copyright ©2018, American Association for Cancer Research.

  9. Antibody-dependent cellular cytotoxicity and skin disease

    International Nuclear Information System (INIS)

    Norris, D.A.; Lee, L.A.

    1985-01-01

    Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). The authors have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. The authors have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, they have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation

  10. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara

    2017-04-01

    Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

  11. Dengue fever

    African Journals Online (AJOL)

    symptoms and research has been limited to studies ... severity and problems with vaccination (4). History of ... Americas in 1970s reduced the spread of dengue fever. After this .... Reiter P. Yellow fever and dengue: a threat to Europe? 9.

  12. Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

    Directory of Open Access Journals (Sweden)

    Katherine L Williams

    2013-02-01

    Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

  13. Immune Response to Dengue and Zika.

    Science.gov (United States)

    Ngono, Annie Elong; Shresta, Sujan

    2018-04-26

    Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell-mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.

  14. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Controversy and debate on dengue vaccine series-paper 1: review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs.

    Science.gov (United States)

    Dans, Antonio L; Dans, Leonila F; Lansang, Mary Ann D; Silvestre, Maria Asuncion A; Guyatt, Gordon H

    2018-03-01

    Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a second time. This is caused by a phenomenon called antibody-dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever-Dengvaxia. The trials in this meta-analysis have been used to campaign for mass vaccination programs in developing countries. We discuss the results of this paper and point out problems in the analyses. Reporting the findings in an Asian trial (CYD14), the authors show a sevenfold rise in one outcome-hospitalization for dengue fever in children <5 years old. However, they fail to point out two signals of harm for another outcome-hospitalization for severe dengue fever (as confirmed by an independent data monitoring committee): 1. In children younger than 9 years, the relative risk was 8.5 (95% confidence interval [CI]: 0.5, 146.8), and 2. In the overall study group, the relative risk was 5.5 (95% CI: 0.9, 33). The authors conduct a subgroup analysis to support claims that the vaccine is probably safe among children aged 9 years or more. This subgroup analysis has limited credibility because: (1) it was a post hoc analysis; (2) it was one of a large number of subgroup analyses; (3) the test of interaction was not reported, but was insignificant (P = 0.14); and (4) there is no biological basis for a threshold age of 9 years. The more likely explanation for the higher risk in younger children is ADE, that is, more frequent seronegativity, rather than age itself. The selective reporting and inappropriate subgroup claims mask the potential harm of dengue mass vaccination

  16. Dengue retinochoroiditis.

    Science.gov (United States)

    Tabbara, Khalid

    2012-01-01

    Dengue is a mosquito-borne infection caused by a flavivirus. I describe the ocular findings observed in two patients infected with dengue virus who presented with acute onset of loss of vision preceded by febrile illness, malaise, generalized fatigue headache, and maculopapular rash. Ophthalmologic evaluation in each patient revealed a normal anterior segment. Vitreous cells were noted in one patient. Ophthalmoscopy revealed multiple foci of retinochoroiditis, vasculitis, cotton-wool spots, and retinal hemorrhages. The healing of the lesion showed discrete atrophic and pigmented retinochoroiditic scars. Fluorescein angiography displayed early hypofluorescence and late hyperfluorescence suggestive of leakage. The healed scars showed late staining. The serologic testing showed elevated IgG antibodies, and one had high IgM antibodies to dengue virus. Ocular findings of dengue fever consist of multifocal areas of retinochoroiditis and may lead to loss of vision. In Saudi Arabia, dengue fever should be considered in the differential diagnosis of multifocal chorioretinal lesions and retinal vasculitis.

  17. A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

    Science.gov (United States)

    Milligan, Gregg N; Sarathy, Vanessa V; White, Mellodee M; Greenberg, M Banks; Campbell, Gerald A; Pyles, Richard B; Barrett, Alan D T; Bourne, Nigel

    2017-10-01

    The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

  18. Reemergence of Dengue in Southern Texas, 2013

    Science.gov (United States)

    Thomas, Dana L.; Santiago, Gilberto A.; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K.; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L.; Smith, Brian; Banicki, Alison; Tomashek, Kay M.; Gaul, Linda

    2016-01-01

    During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico. PMID:27191223

  19. Potential anti-Dengue Concoction of Carica Papaya (C. Papaya) Leaf and G. Mangostana (G. Mangostana) Pericarp and Their Bioactivity Enhancement by Fermentation: A Review

    Science.gov (United States)

    So’aib, M. S.; Salihon, J.; Tan, H. L.

    2018-05-01

    This review highlights the anti-dengue potency of Carica Papaya leaf (CPL) extract which was associated with platelet increase and other medicinal properties such as antiinflammatory and antioxidant. Garcinia Mangostana’s pericarp (GMP) extract have much commonalities with CPL, in addition to antiviral and immunomodulatory properties of the former. These properties may exhibit, yet unproven, analgesic, hemorrhage prevention and antiviral effects that may facilitate dengue recovery. Nevertheless, the limited bioavailability of native polyphenolic contents of both, as hinted by studies on colonic microbiome metabolism on dietary polyphenols, highlighted fermentation as viable method to enhance the functionality of the compounds. Thus, this review also highlights some relevant parameters in existing fermentation of well known fermented foods that impact their bioactivity, functionality and palatability that may applicable for the development of CPL and GMP fermentations.

  20. Enhanced sensing of dengue virus DNA detection using O{sub 2} plasma treated-silicon nanowire based electrical biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, S.F.A., E-mail: siti_fatimah0410@yahoo.com [Institute of Advanced Technology, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor (Malaysia); Yusof, N.A., E-mail: azahy@upm.edu.my [Institute of Advanced Technology, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor (Malaysia); Chemistry Department, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor (Malaysia); Hashim, U. [Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Hushiarian, R. [La Trobe Institute for Molecular Science, La Trobe University, Victoria, 3086 (Australia); Nuzaihan, M.N.M. [Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Hamidon, M.N. [Institute of Advanced Technology, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor (Malaysia); Zawawi, R.M. [Chemistry Department, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor (Malaysia); Fathil, M.F.M. [Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia)

    2016-10-26

    Dengue Virus (DENV) has become one of the most serious arthropod-borne viral diseases, causing death globally. The existing methods for DENV detection suffer from the late stage treatment due to antibodies-based detection which is feasible only after five days following the onset of the illness. Here, we demonstrated the highly effective molecular electronic based detection utilizing silicon nanowire (SiNW) integrated with standard complementary metal-oxide-semiconductor (CMOS) process as a sensing device for detecting deoxyribonucleic acid (DNA) related to DENV in an early stage diagnosis. To transform the fabricated devices as a functional sensing element, three-step procedure consist of SiNW surface modification, DNA immobilization and DNA hybridization were employed. The detection principle works by detecting the changes in current of SiNW which bridge the source and drain terminal to sense the immobilization of probe DNA and their hybridization with target DNA. The oxygen (O{sub 2}) plasma was proposed as an effective strategy for increasing the binding amounts of target DNA by modified the SiNW surface. It was found that the detection limit of the optimized O{sub 2} plasma treated-SiNW device could be reduced to 1.985 × 10{sup −14} M with a linear detection range of the sequence-specific DNA from 1.0 × 10{sup −9} M to 1.0 × 10{sup −13} M. In addition, the developed biosensor device was able to discriminate between complementary, single mismatch and non-complementary DNA sequences. This highly sensitive assay was then applied to the detection of reverse transcription-polymerase chain reaction (RT-PCR) product of DENV-DNA, making it as a potential method for disease diagnosis through electrical biosensor. - Highlights: • Molecular electronic detection of Dengue Virus (DENV) DNA using SiNW biosensor is presented. • Oxygen plasma surface treatment as an enhancer technique for device sensitivity is highlighted. • The limit of detection (Lo

  1. Enhanced sensing of dengue virus DNA detection using O_2 plasma treated-silicon nanowire based electrical biosensor

    International Nuclear Information System (INIS)

    Rahman, S.F.A.; Yusof, N.A.; Hashim, U.; Hushiarian, R.; Nuzaihan, M.N.M.; Hamidon, M.N.; Zawawi, R.M.; Fathil, M.F.M.

    2016-01-01

    Dengue Virus (DENV) has become one of the most serious arthropod-borne viral diseases, causing death globally. The existing methods for DENV detection suffer from the late stage treatment due to antibodies-based detection which is feasible only after five days following the onset of the illness. Here, we demonstrated the highly effective molecular electronic based detection utilizing silicon nanowire (SiNW) integrated with standard complementary metal-oxide-semiconductor (CMOS) process as a sensing device for detecting deoxyribonucleic acid (DNA) related to DENV in an early stage diagnosis. To transform the fabricated devices as a functional sensing element, three-step procedure consist of SiNW surface modification, DNA immobilization and DNA hybridization were employed. The detection principle works by detecting the changes in current of SiNW which bridge the source and drain terminal to sense the immobilization of probe DNA and their hybridization with target DNA. The oxygen (O_2) plasma was proposed as an effective strategy for increasing the binding amounts of target DNA by modified the SiNW surface. It was found that the detection limit of the optimized O_2 plasma treated-SiNW device could be reduced to 1.985 × 10"−"1"4 M with a linear detection range of the sequence-specific DNA from 1.0 × 10"−"9 M to 1.0 × 10"−"1"3 M. In addition, the developed biosensor device was able to discriminate between complementary, single mismatch and non-complementary DNA sequences. This highly sensitive assay was then applied to the detection of reverse transcription-polymerase chain reaction (RT-PCR) product of DENV-DNA, making it as a potential method for disease diagnosis through electrical biosensor. - Highlights: • Molecular electronic detection of Dengue Virus (DENV) DNA using SiNW biosensor is presented. • Oxygen plasma surface treatment as an enhancer technique for device sensitivity is highlighted. • The limit of detection (LoD) as low as 1.985

  2. Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

  3. Dengue Returns

    Centers for Disease Control (CDC) Podcasts

    2016-08-25

    Dr. Tyler Sharp, a CDC epidemiologist, discusses dengue in southern Texas.  Created: 8/25/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/25/2016.

  4. Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice

    Science.gov (United States)

    Jaiswal, Smita; Pazoles, Pamela; Woda, Marcia; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2012-01-01

    Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections. PMID:22384859

  5. Dengue Fever: Causes, Complications, and Vaccine Strategies

    Directory of Open Access Journals (Sweden)

    Niyati Khetarpal

    2016-01-01

    Full Text Available Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur’s chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.

  6. Dengue perinatal

    Directory of Open Access Journals (Sweden)

    Doris Martha Salgado

    2013-08-01

    Full Text Available El dengue es en la actualidad la enfermedad viral más relevante de transmisión vectorial hiperendémica en las Américas. El incremento en el número de casos se ha relacionado con la aparición de dengue durante la gestación y en el periodo neonatal. De acuerdo con la edad de gestación en la que ocurra la infección, podrían presentarse manifestaciones en el feto, como aborto, y en los pacientes a término,dengue neonatal. En este artículo se presenta una reseña de los casos reportados a nivel mundial, y especialmente en las Américas, así como aspectos fisiopatogénicos de la enfermedad.   doi: http://dx.doi.org/10.7705/biomedica.v33i0.1449

  7. Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.

    Science.gov (United States)

    Dutta, Shovan; Celestine, Michael J; Khanal, Supreet; Huddleston, Alexis; Simms, Colin; Arca, Jessa Faye; Mitra, Amlan; Heller, Loree; Kraj, Piotr J; Ledizet, Michel; Anderson, John F; Neelakanta, Girish; Holder, Alvin A; Sultana, Hameeda

    2018-01-01

    Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100μM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen) 2 ]Cl 2 , (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen) 3 ]Cl 3 , (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl 2 ·2H 2 O) or cobalt(II) chloride hexahydrate (CoCl 2 ·6H 2 O) alone had no effects as "free" cations

  8. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  9. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2016-02-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  10. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2010-08-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  11. Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

    Directory of Open Access Journals (Sweden)

    Trai-Ming Yeh

    Full Text Available Dengue virus (DV infections cause mild dengue fever (DF or severe life-threatening dengue hemorrhagic fever (DHF. The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM and macrophage migration inhibitory factor (MIF are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM and intercellular adhesion molecule-1 (ICAM-1 in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

  12. Screening of anti-dengue activity in methanolic extracts of medicinal plants

    Directory of Open Access Journals (Sweden)

    Tang Leon IC

    2012-01-01

    Full Text Available Abstract Background Dengue fever regardless of its serotypes has been the most prevalent arthropod-borne viral diseases among the world population. The development of a dengue vaccine is complicated by the antibody-dependent enhancement effect. Thus, the development of a plant-based antiviral preparation promises a more potential alternative in combating dengue disease. Methods Present studies investigated the antiviral effects of standardised methanolic extracts of Andrographis paniculata, Citrus limon, Cymbopogon citratus, Momordica charantia, Ocimum sanctum and Pelargonium citrosum on dengue virus serotype 1 (DENV-1. Results O. sanctum contained 88.6% of total flavonoids content, an amount that was the highest among all the six plants tested while the least was detected in M. charantia. In this study, the maximum non-toxic dose (MNTD of the six medicinal plants was determined by testing the methanolic extracts against Vero E6 cells in vitro. Studies also determined that the MNTD of methanolic extract was in the decreasing order of M. charantia >C. limon >P. citrosum, O. sanctum >A. paniculata >C. citratus. Antiviral assay based on cytopathic effects (CPE denoted by degree of inhibition upon treating DENV1-infected Vero E6 cells with MNTD of six medicinal plants showed that A. paniculata has the most antiviral inhibitory effects followed by M. charantia. These results were further verified with an in vitro inhibition assay using MTT, in which 113.0% and 98.0% of cell viability were recorded as opposed to 44.6% in DENV-1 infected cells. Although methanolic extracts of O. sanctum and C. citratus showed slight inhibition effect based on CPE, a significant inhibition was not reflected in MTT assay. Methanolic extracts of C. limon and P. citrosum did not prevent cytopathic effects or cell death from DENV-1. Conclusions The methanol extracts of A. paniculata and M. charantia possess the ability of inhibiting the activity of DENV-1 in in vitro assays

  13. Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

    Science.gov (United States)

    2015-05-18

    flaviviruses (e.g., Japanese encephalitis and yellow fever viruses) have on DENV transmission and the observed clinical phenotypes following...Initiate case identification and evaluation. KAVRU provides the KPPPH dengue diagnostic research assays for patients presenting with fever or history of...Scott RM, Thomas SJ, Hoke CH Jr, 2013. A model international partnership for community-based research on vaccine -preventable diseases: the Kamphaeng

  14. Roles for Endothelial Cells in Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Nadine A. Dalrymple

    2012-01-01

    Full Text Available Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

  15. Severe Dengue Fever Outbreak in Taiwan.

    Science.gov (United States)

    Wang, Sheng-Fan; Wang, Wen-Hung; Chang, Ko; Chen, Yen-Hsu; Tseng, Sung-Pin; Yen, Chia-Hung; Wu, Deng-Chyang; Chen, Yi-Ming Arthur

    2016-01-01

    Dengue fever (DF) is a vector-borne disease caused by dengue viruses (DENVs). Epidemic dengue occurs intermittently in Taiwan. In 2014, Taiwan experienced its largest DF outbreak. There were 15,732 DF cases reported. There were a total of 136 dengue hemorrhagic fever (DHF) cases, of which 20 resulted in death. Most DF cases were reported in southern Taiwan. A total of 15,043 (96%) cases were from Kaohsiung, a modern city in southern Taiwan. This report reviews DF epidemics in Taiwan during 2005-2014. The correlation between DF and DHF along with temperature and precipitation were conjointly examined. We conclude that most dengue epidemics in Taiwan resulted from imported DF cases. Results indicate three main factors that may have been associated with this DF outbreak in Kaohsiung: an underground pipeline explosion combined with subsequent rainfall and higher temperature. These factors may have enhanced mosquito breeding activity, facilitating DENV transmission. © The American Society of Tropical Medicine and Hygiene.

  16. Research on Climate and Dengue in Malaysia: A Systematic Review.

    Science.gov (United States)

    Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rocklöv, Joacim

    2016-03-01

    Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based dengue early warning system in a dengue-endemic country, taking Malaysia as a case study. We reviewed the relationship between climate and dengue derived from statistical modeling, laboratory tests, and field studies. We searched electronic databases including PubMed, Scopus, EBSCO (MEDLINE), Web of Science, and the World Health Organization publications, and assessed climate factors and their influence on dengue cases, mosquitoes, and virus and recent development in the field of climate and dengue. Few studies in Malaysia have emphasized the relationship between climate and dengue. Climatic factors such as temperature, rainfall, and humidity are associated with dengue; however, these relationships were not consistent. Climate change projections for Malaysia show a mounting risk for dengue in the future. Scientific studies on climate and dengue enhance dengue surveillance in the long run. It is essential for institutions in Malaysia to promote research on climate and vector-borne diseases to advance the development of climate-based early warning systems. Together, effective strategies that improve existing research capacity, maximize the use of limited resources, and promote local-international partnership are crucial for sustaining research on climate and health.

  17. FcγRII-binding Centyrins mediate agonism and antibody-dependent cellular phagocytosis when fused to an anti-OX40 antibody.

    Science.gov (United States)

    Zhang, Di; Whitaker, Brian; Derebe, Mehabaw G; Chiu, Mark L

    2018-04-01

    Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR) are emerging as promising cancer immunotherapies. The agonism activity of such antibodies depends on crosslinking to Fc gamma RIIB receptor (FcγRIIB) to enable the antibody multimerization that drives TNFR activation. Previously, Fc engineering was used to enhance the binding of such antibodies to Fcγ receptors. Here, we report the identification of Centyrins as alternative scaffold proteins with binding affinities to homologous FcγRIIB and FcγRIIA, but not to other types of Fcγ receptors. One Centyrin, S29, was engineered at distinct positions of an anti-OX40 SF2 antibody to generate bispecific and tetravalent molecules named as mAbtyrins. Regardless of the position of S29 on the SF2 antibody, SF2-S29 mAbtyrins could bind FcγRIIB and FcγRIIA specifically while maintaining binding to OX40 receptors. In a NFκB reporter assay, attachment of S29 Centyrin molecules at the C-termini, but not the N-termini, resulted in SF2 antibodies with increased agonism owing to FcγRIIB crosslinking. The mAbtyrins also showed agonism in T-cell activation assays with immobilized FcγRIIB and FcγRIIA, but this activity was confined to mAbtyrins with S29 specifically at the C-termini of antibody heavy chains. Furthermore, regardless of the position of the molecule, S29 Centyrin could equip an otherwise Fc-silent antibody with antibody-dependent cellular phagocytosis activity without affecting the antibody's intrinsic antibody-dependent cell-meditated cytotoxicity and complement-dependent cytotoxicity. In summary, the appropriate adoption FcγRII-binding Centyrins as functional modules represents a novel strategy to engineer therapeutic antibodies with improved functionalities.

  18. ADE and dengue vaccination.

    Science.gov (United States)

    Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José

    2017-07-13

    The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Antibody Prophylaxis Against Dengue Virus 2 Infection in Non-Human Primates.

    Science.gov (United States)

    Simmons, Monika; Putnak, Robert; Sun, Peifang; Burgess, Timothy; Marasco, Wayne A

    2016-11-02

    Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (FcγR) and potentiate antibody-dependent enhancement (ADE). In the first experiment, groups of animals received ISG or Mab11/wt at low doses (3-10 mg/kg) or a saline control followed by challenge with DENV-2 at day 10 or 30. After passive immunization, only low-titered circulating virus-neutralizing antibody titers were measured in both groups, which were undetectable by day 30. After challenge at day 10, a reduction in viremia duration compared with the control was seen only in the ISG group (75%). However, after a day 30 challenge, no reduction in viremia was observed in both immunized groups. In a second experiment to test the effect of higher antibody doses on short-term protection, groups received either ISG, Mab11/wt, Mab11/mutFc (each at 25 mg/kg) or saline followed by challenge with DENV-2 on day 10. Increased virus-neutralizing antibody titers were detected in all groups at day 5 postinjection, with geometric mean titers (GMTs) of 464 (ISG), 313 (Mab11/wt), and 309 (Mab11/mutFc). After challenge, there was complete protection against viremia in the group that received ISG, and a reduction in viremia duration of 89% and 83% in groups that received Mab11/wt and Mab11/mutFc, respectively. An in vitro ADE assay in Fcγ receptor-bearing K562 cells with sera collected immediately before challenge showed increased DENV-2 infection levels in the presence of both ISG and Mab11/wt, which peaked at a

  20. Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210.

    Science.gov (United States)

    Watanabe, M; Wallace, P K; Keler, T; Deo, Y M; Akewanlop, C; Hayes, D F

    1999-02-01

    MDX-210 is a bispecific antibody (BsAb) with specificity for both the proto-oncogene product of HER-2/neu (c-erbB-2) and FcgammaRI (CD64). HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcgammaRI is expressed on human monocytes, macrophages, and IFN-gamma activated granulocytes. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by human monocyte-derived macrophages (MDM) mediated by BsAb MDX-210, its partially humanized derivative (MDX-H210), and its parent MoAb 520C9 (anti-HER-2/neu) under various conditions. Purified monocytes were cultured with GM-CSF, M-CSF, or no cytokine for five or six days. Antibody dependent cellular phagocytosis (ADCP) and cytolysis (ADCC) assays were performed with the MDM and HER-2/neu positive target cells (SK-BR-3). ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and phycoerythrin-conjugated (red) monoclonal antibodies (MoAb) against human CD14 and CD11b. ADCC was measured with a non-radioactive LDH detection kit. Both BsAb MDX-210 (via FcgammaRI) and MoAb 520C9 (mouse IgG1, via FcgammaRII) mediated similar levels of ADCP and ADCC. ADCP mediated by BsAb MDX-H210 was identical to that mediated by BsAb MDX-210. Confocal microscopy demonstrated that dual-labeled cells represented true phagocytosis. Both ADCP and ADCC were higher when MDM were pre-incubated with GM-CSF than when incubated with M-CSF. BsAb MDX-210 is as active in vitro as the parent MoAb 520C9 in inducing both phagocytosis and cytolysis of MDM. MDX-210 and its partially humanized derivative, MDX-H210, mediated similar levels of ADCP. GM-CSF appears to superior to M-CSF in inducing MDM-mediated ADCC and ADCP. These studies support the ongoing clinical investigations of BsAb MDX-210 and its partially humanized derivative.

  1. Dengue encephalitis–A rare manifestation of dengue fever

    OpenAIRE

    Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nityananda; Laxman, Mridula; Mahalingam, Soundarya

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with...

  2. Dengue Fever/Dengue Haemorrhagic Fever : Case Management

    OpenAIRE

    Nimmannitya, Suchitra

    1995-01-01

    Dengue infections caused by the four antigenically distinct dengue virus serotypes (dengue virus 1, dengue virus 2, dengue virus 3, dengue virus 4) of the family Flavivindae, are the most important arbovirus disease in man, both in terms of morbidity and mortality. The infection is transmitted from man to man by Aedes mosquitoes. Since 1956, dengue virus infection has resulted in more than 3 million hospital admissions and more than 50,000 deaths in Southeast Asia, Western Pacific countries, ...

  3. Dengue fever (image)

    Science.gov (United States)

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  4. Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis.

    Science.gov (United States)

    Ashraf, S Q; Umana, P; Mössner, E; Ntouroupi, T; Brünker, P; Schmidt, C; Wilding, J L; Mortensen, N J; Bodmer, W F

    2009-11-17

    The effect of glycoengineering a membrane specific anti-carcinoembryonic antigen (CEA) (this paper uses the original term CEA for the formally designated CEACAM5) antibody (PR1A3) on its ability to enhance killing of colorectal cancer (CRC) cell lines by human immune effector cells was assessed. In vivo efficacy of the antibody was also tested. The antibody was modified using EBNA cells cotransfected with beta-1,4-N-acetylglucosaminyltransferase III and the humanised hPR1A3 antibody genes. The resulting alteration of the Fc segment glycosylation pattern enhances the antibody's binding affinity to the FcgammaRIIIa receptor on human immune effector cells but does not alter the antibody's binding capacity. Antibody-dependent cellular cytotoxicity (ADCC) is inhibited in the presence of anti-FcgammaRIII blocking antibodies. This glycovariant of hPR1A3 enhances ADCC 10-fold relative to the parent unmodified antibody using either unfractionated peripheral blood mononuclear or natural killer (NK) cells and CEA-positive CRC cells as targets. NK cells are far more potent in eliciting ADCC than either freshly isolated monocytes or granulocytes. Flow cytometry and automated fluorescent microscopy have been used to show that both versions of hPR1A3 can induce antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages. However, the glycovariant antibody did not mediate enhanced ADCP. This may be explained by the relatively low expression of FcgammaRIIIa on cultured macrophages. In vivo studies show the efficacy of glycoengineered humanised IgG1 PR1A3 in significantly improving survival in a CRC metastatic murine model. The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.

  5. Enhanced severity of secondary dengue-2 infections: death rates in 1981 and 1997 Cuban outbreaks Aumento de la gravedad de las infecciones secundarias por dengue-2: tasas de mortalidad en los brotes cubanos de 1981 y 1997

    Directory of Open Access Journals (Sweden)

    María G. Guzmán

    2002-04-01

    Full Text Available Objective. To understand the possible effect that length of time has on disease severity with sequential dengue infections. Methods. Death and hospitalization rates for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS per 10 000 secondary dengue-2 infections were compared in the same age group for two dengue-2 (DEN-2 epidemics in Cuba. The first DEN-2 epidemic affected all of Cuba in 1981; the second one, in 1997, impacted only the city of Santiago de Cuba. The sensitizing infection for DHF/DSS for each of the DEN-2 epidemics was dengue-1 (DEN-1 serotype virus, which was transmitted in 1977-1979, that is, 4 years and 20 years before the two DEN-2 epidemics. Using published seroepidemiological data from the cities of Havana and Santiago de Cuba, we estimated the rates at which persons aged 15-39 years old and those 40 years and older were hospitalized or died of DHF/DSS in Havana and in all of Cuba in 1981 and in just Santiago de Cuba in 1997. Results. Among adults 15-39 years old the death rate per 10 000 secondary DEN-2 infections was 38.5 times as high in Santiago de Cuba in 1997 as in Havana in 1981. As a further indication of the increased severity coming with a longer period between the initial DEN-1 infection and the secondary DEN-2 infection, the case fatality rate for that same age group was 4.7 times as high in Santiago in 1997 as it was in Havana in 1981. Conclusion. We found a marked increase in severity with the longer of the two intervals (20 years between an initial DEN-1 infection and a secondary DEN-2 infection. Such a difference may be due to subtle shifts in causative dengue strains or to changes with the passage of time in the circulating population of human dengue antibodies. These observations have important implications for dengue control, pathogenic mechanisms, and vaccine development.Objetivos. Investigar el posible efecto del tiempo sobre la gravedad de la enfermedad en sucesivas infecciones por dengue. M

  6. Psychosis in dengue fever

    OpenAIRE

    Suprakash Chaudhury; Biswajit Jagtap; Deepak Kumar Ghosh

    2017-01-01

    An 18-year-old male student developed abnormal behavior while undergoing treatment for dengue fever. He was ill-kempt, irritable and had auditory and visual hallucinations and vague persecutory delusions in clear sensorium with impaired insight. The psychotic episode had a temporal correlation with dengue fever. Psychiatric comorbidities of dengue fever including mania, anxiety, depression, and catatonia are mentioned in literature but the literature on the psychosis following dengue is spars...

  7. Post-dengue parkinsonism

    OpenAIRE

    Azmin, Shahrul; Sahathevan, Ramesh; Suehazlyn, Zainudin; Law, Zhe Kang; Rabani, Remli; Nafisah, Wan Yahya; Tan, Hui Jan; Norlinah, Mohamed Ibrahim

    2013-01-01

    Background Dengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature. Case presentation A previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations. Conclusions The authors...

  8. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  9. Dengue in children

    NARCIS (Netherlands)

    Verhagen, L.M.; Groot, R. de

    2014-01-01

    Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with

  10. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.

    Science.gov (United States)

    Halstead, Scott B

    2017-07-17

    The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  11. The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral replication in normal out-bred mice resulting in lethal multi-organ disease.

    Directory of Open Access Journals (Sweden)

    Andrew K I Falconar

    Full Text Available Antibody-enhanced replication (AER of dengue type-2 virus (DENV-2 strains and production of antibody-enhanced disease (AED was tested in out-bred mice. Polyclonal antibodies (PAbs generated against the nonstructural-1 (NS1 glycoprotein candidate vaccine of the New Guinea-C (NG-C or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD₅₀ of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS, displayed by diffuse alveolar damage (DAD resulting from i dramatic interstitial alveolar septa-thickening with mononuclear cells, ii some hyperplasia of alveolar type-II pneumocytes, iii copious intra-alveolar protein secretion, iv some hyaline membrane-covered alveolar walls, and v DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human "severe dengue" cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines

  12. Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Ootsubo, Michiko; Izawa, Ken-ichi; Kohroki, Junya; Masuho, Yasuhiko

    2016-01-01

    The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  13. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  14. Research on Climate and Dengue in Malaysia: A Systematic Review

    OpenAIRE

    Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rockl?v, Joacim

    2016-01-01

    Background & Objectives Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based de...

  15. 18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

    Science.gov (United States)

    Chacko, Ann-Marie; Watanabe, Satoru; Herr, Keira J; Kalimuddin, Shirin; Tham, Jing Yang; Ong, Joanne; Reolo, Marie; Serrano, Raymond M F; Cheung, Yin Bun; Low, Jenny G H; Vasudevan, Subhash G

    2017-05-04

    Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection-associated inflammation biomarker for assessing treatment response during therapeutic intervention trials.

  16. Dengue in children.

    Science.gov (United States)

    Verhagen, Lilly M; de Groot, Ronald

    2014-11-01

    Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with secondary heterologous dengue infections are most at risk for severe dengue disease. Laboratory diagnosis of dengue can be established within five days of disease onset by direct detection of viral components in serum. After day five, serologic diagnosis provides indirect evidence of dengue. Currently, no effective antiviral agents are available to treat dengue infection. Therefore, treatment remains supportive, with emphasis on close hematological monitoring, recognition of warning signs of severe disease and fluid-replacement therapy and/or blood transfusions when required. Development of a dengue vaccine is considered a high public health priority. A safe and efficacious dengue vaccine would also be important for travelers. This review highlights the current understanding of dengue in children, including its clinical manifestations, pathogenesis, diagnostic tests, management and prevention. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. Substitution of wild-type yellow fever Asibi sequences for 17D vaccine sequences in ChimeriVax-dengue 4 does not enhance infection of Aedes aegypti mosquitoes.

    Science.gov (United States)

    McGee, Charles E; Tsetsarkin, Konstantin; Vanlandingham, Dana L; McElroy, Kate L; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen

    2008-03-01

    To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax-dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field-collected and laboratory-colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low-level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal.

  18. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  19. Antibody-dependent NK cell activation is associated with late kidney allograft dysfunction and the complement-independent alloreactive potential of donor-specific antibodies

    Directory of Open Access Journals (Sweden)

    Tristan Legris

    2016-08-01

    Full Text Available Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs. The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK cells as innate immune effectors of antibody-dependent cellular cytotoxicity, but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years. Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate (eGFR over a 1-year period (hazard ratio: 2.83. In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration

  20. Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

    Science.gov (United States)

    Manchala, Nageswar Reddy; Dungdung, Ranjeet; Pilankatta, Rajendra

    2017-10-01

    Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. © 2017 John Wiley & Sons Ltd.

  1. Dengue and dengue haemorrhagic fever: Indian perspective

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    mainly in children (Halstead 2002, 2007; Chaturvedi and. Shrivastava 2004). Dengue ... of molecular epidemiology, immunopathology and vaccine development. Selected work done in ..... Only the Indian initiative in this field is presented here.

  2. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  3. Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Ellegaard, J

    1981-01-01

    This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunolog...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

  4. An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions.

    Science.gov (United States)

    Kinder, Michelle; Greenplate, Allison R; Strohl, William R; Jordan, Robert E; Brezski, Randall J

    2015-01-01

    Cytotoxic therapeutic monoclonal antibodies (mAbs) often mediate target cell-killing by eliciting immune effector functions via Fc region interactions with cellular and humoral components of the immune system. Key functions include antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). However, there has been increased appreciation that along with cell-killing functions, the induction of antibody-dependent cytokine release (ADCR) can also influence disease microenvironments and therapeutic outcomes. Historically, most Fc engineering approaches have been aimed toward modulating ADCC, ADCP, or CDC. In the present study, we describe an Fc engineering approach that, while not resulting in impaired ADCC or ADCP, profoundly affects ADCR. As such, when peripheral blood mononuclear cells are used as effector cells against mAb-opsonized tumor cells, the described mAb variants elicit a similar profile and quantity of cytokines as IgG1. In contrast, although the variants elicit similar levels of tumor cell-killing as IgG1 with macrophage effector cells, the variants do not elicit macrophage-mediated ADCR against mAb-opsonized tumor cells. This study demonstrates that Fc engineering approaches can be employed to uncouple macrophage-mediated phagocytic and subsequent cell-killing functions from cytokine release.

  5. Dengue-associated kidney disease.

    Science.gov (United States)

    Lizarraga, Karlo J; Nayer, Ali

    2014-01-01

    A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. In the vast majority of cases, dengue infection and associated renal disorders are self-limited.

  6. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Directory of Open Access Journals (Sweden)

    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  7. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  8. Post dengue neurological complication

    Directory of Open Access Journals (Sweden)

    Hizlinda Tohid

    2015-12-01

    Full Text Available Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain–Barre syndrome (GBS is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE followed by an upper respiratory tract infection (URTI weeks prior to her presentation rendering GBS secondary to the post viral URTI and AGE as the most likely diagnosis. Presence of thrombocytopenia was the only clue for dengue in this case.

  9. T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

    Directory of Open Access Journals (Sweden)

    Dominic Paquin-Proulx

    2017-06-01

    Full Text Available Background: The outbreak of Zika virus (ZIKV infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV, or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE, suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT. Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

  10. T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus.

    Science.gov (United States)

    Paquin-Proulx, Dominic; Leal, Fabio E; Terrassani Silveira, Cassia G; Maestri, Alvino; Brockmeyer, Claudia; Kitchen, Shannon M; Cabido, Vinicius D; Kallas, Esper G; Nixon, Douglas F

    2017-01-01

    The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNγ ELISPOT. Three peptides induced IFNγ production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

  11. Epidemiologi dan Diagnosis Dengue di Indonesia

    OpenAIRE

    Zilhadia, Zilhadia

    2007-01-01

    Dengue fever/DF and dengue hemorrhagic fever/DHF is a global public health problem that occured in tropical and subtropical region. Epidemic dengue occurs every years, and it continues to be a major health problem in Indonesia. Due to its asymptomatic nature, a reliable, rapid and accurate dengue diagnosis is needed. Dengue diagnosis method based on molecular dengue virus properties and it will be developed by researcher. Dengue rapid test isnewly method. This article explaine about dengue ep...

  12. Assessing the methods needed for improved dengue mapping: a SWOT analysis.

    Science.gov (United States)

    Attaway, David Frost; Jacobsen, Kathryn H; Falconer, Allan; Manca, Germana; Waters, Nigel M

    2014-01-01

    Dengue fever, a mosquito-borne viral infection, is a growing threat to human health in tropical and subtropical areas worldwide. There is a demand from public officials for maps that capture the current distribution of dengue and maps that analyze risk factors to predict the future burden of disease. To identify relevant articles, we searched Google Scholar, PubMed, BioMed Central, and WHOLIS (World Health Organization Library Database) for published articles with a specific set of dengue criteria between January 2002 and July 2013. After evaluating the currently available dengue models, we identified four key barriers to the creation of high-quality dengue maps: (1) data limitations related to the expense of diagnosing and reporting dengue cases in places where health information systems are underdeveloped; (2) issues related to the use of socioeconomic proxies in places with limited dengue incidence data; (3) mosquito ranges which may be changing as a result of climate changes; and (4) the challenges of mapping dengue events at a variety of scales. An ideal dengue map will present endemic and epidemic dengue information from both rural and urban areas. Overcoming the current barriers requires expanded collaboration and data sharing by geographers, epidemiologists, and entomologists. Enhanced mapping techniques would allow for improved visualizations of dengue rates and risks.

  13. Dengue, Zika y Chikungunya

    OpenAIRE

    Kantor, Isabel N

    2016-01-01

    Los responsables de la actual pandemia de Chikungunya (alfavirus), dengue y Zika (flavivirus) son virus trasmitidos por artrópodos, arbovirus. Su importancia aumentó en las Américas en los últimos 20 años. Los vectores principales son Aedes aegypti y A. albopictus. La infección por dengue provee inmunidad duradera al serotipo específico y temporaria a otros tres. La posterior infección por otro serotipo determina mayor gravedad. Existe una vacuna contra dengue registrada, Dengvaxia (Sanofi Pa...

  14. Dengue: a reappraisal

    OpenAIRE

    Serufo, José Carlos; Nobre, Vandack; Rayes, Abdunnabi; Marcial, Tânia Maria; Lambertucci, José Roberto

    2000-01-01

    Os conceitos de dengue clássico, com ou sem hemorragia, e de febre hemorrágica do dengue (FHD) que, pode cursar sem fenômenos hemorrágicos, com ou sem síndrome do choque do dengue (SCD), são revistos neste artigo. As definições clássicas propostas, úteis em outros tempos, geram confusão e dificultam a tomada de decisões no momento do tratamento dos pacientes com as formas graves da doença porque deixaram de incorporar novos conceitos e avanços terapêuticos. A classificação do dengue proposta ...

  15. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G

    2012-01-01

    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage...... of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...... of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue....

  16. Treatment of dengue fever

    OpenAIRE

    Rajapakse, Senaka; Rodrigo,Chaturaka; Rajapakse,Anoja Chamarie

    2012-01-01

    Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decad...

  17. Dengue en Colombia

    Directory of Open Access Journals (Sweden)

    Jorge Boshell

    1986-12-01

    Full Text Available El Gobierno Colombiano estableció una campaña que erradicó el Aedes aegypti de su territorio en atención a las recomendaciones que hizo la Oficina Sanitaria Panamericana en 1947. Esta campaña consiguió desaparecer el dengue endémico durante aproximadamente 20 años, apareciendo de nuevo en forma explosiva con la epidemia de dengue 2 en la Costa Atlántica (1971-1972, seguida de dos epidemias bien documentadas de dengue 3 (1975-1977 y dengue 1 en 1978. Se hace un resumen de las actividades que desarrolla el Laboratorio de Virología del Instituto Nacional de Salud para apoyar el diagnóstico de esta enfermedad en el país incluyendo el primer aislamiento de dengue 4 en 1982, la actividad de los virus dengue 1, 2 y 4 detectada hasta la fecha, los hallazgos clínicos y virológicos en un caso fatal de enfermedad hemorrágica asociada a infección por virus del dengue y un breve recuento de la epidemia de Tumaco en la Costa Pacífica en la cual se comprobó actividad simultánea de dengue 1 y 2. Finalmente se informa sobre el estado de infestación que tiene el país actualmente con el Aedes aegypti y sobre la actividad del virus de fiebre amarilla en focos selváticos vecinos a ciudades altamente infestadas, detectada en el mes de enero de 1987 en Colombia.

  18. Forecast of dengue incidence using temperature and rainfall.

    Directory of Open Access Journals (Sweden)

    Yien Ling Hii

    Full Text Available An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore.We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98% in 2004-2010 and 98% (CI = 95%-100% in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm.We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.

  19. Forecast of dengue incidence using temperature and rainfall.

    Science.gov (United States)

    Hii, Yien Ling; Zhu, Huaiping; Ng, Nawi; Ng, Lee Ching; Rocklöv, Joacim

    2012-01-01

    An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore. We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98%) in 2004-2010 and 98% (CI = 95%-100%) in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm. We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.

  20. Treatment of dengue fever

    Directory of Open Access Journals (Sweden)

    Rajapakse S

    2012-07-01

    Full Text Available Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decades at an alarming rate. In the endemic areas, waves of infection occur in epidemics, with thousands of individuals affected, creating a huge burden on the limited resources of a country's health care system. While the illness passes off as a simple febrile episode in many, a few have a severe illness marked by hypovolemic shock and bleeding. Iatrogenic fluid overload in the management may further complicate the picture. In this severe form dengue can be fatal. Tackling the burden of dengue is impeded by several issues, including a lack of understanding about the exact pathophysiology of the infection, inability to successfully control the vector population, lack of specific therapy against the virus, and the technical difficulties in developing a vaccine. This review provides an overview on the epidemiology, natural history, management strategies, and future directions for research on dengue, including the potential for development of a vaccine.Keywords: dengue, treatment, fluid resuscitation

  1. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients.

    Science.gov (United States)

    Petricevic, Branka; Laengle, Johannes; Singer, Josef; Sachet, Monika; Fazekas, Judit; Steger, Guenther; Bartsch, Rupert; Jensen-Jarolim, Erika; Bergmann, Michael

    2013-12-12

    Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to

  2. Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells.

    Science.gov (United States)

    Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R; Gulley, James L; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-10-01

    Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. ©2015 American Association for Cancer Research.

  3. Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

    Science.gov (United States)

    Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-01-01

    Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L1 MAb would potentially be able to block PD-L1/PD1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 MAb. The studies reported here demonstrate (a) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (b) IFNγ can enhance tumor cell PD-L1 expression and in some cases enhance ADCC tumor cell lysis; (c) purified NK cells are potent effectors for avelumab; (d) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (e) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (f) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 MAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. PMID:26014098

  4. Associations between Dengue Hospitalizations and Climate in Can Tho, Vietnam, 2001-2011

    Directory of Open Access Journals (Sweden)

    Nguyen P. Toai

    2016-07-01

    Full Text Available In Vietnam, dengue fever is a major cause of hospitalization with over one million cases reported between 1991 and 2004. Changes in the incidence of dengue in Can Tho city due to increased temperature and changes in precipitation, are anticipated. In an effort to better characterize the relationship between climate and dengue, we examine the associations between weather variables and dengue hospitalizations in Can Tho between 2001 and 2011. Monthly data on hospitalized dengue cases and means of temperature, rainfall and humidity were recorded from 2001 to 2011. We used the Box-Jenkins approach to modelling of time series to assess the association between these factors. This model was validated by the Portmanteau test. Our results revealed that the highest dengue incidences in Can Tho occur between July and December. After adjusting for seasonality, the rate of dengue hospitalizations was significantly associated with relative humidity with a lag of one month. Rainfall and temperature were not predictors of dengue hospitalization rate. In conclusion, these data suggest that maximum relative humidity (with a one month lag is an important determinant of dengue hospitalizations. Enhanced vector control during months with high humidity may be an important approach to prevent dengue transmission.

  5. An in-depth analysis of original antigenic sin in dengue virus infection.

    Science.gov (United States)

    Midgley, Claire M; Bajwa-Joseph, Martha; Vasanawathana, Sirijitt; Limpitikul, Wannee; Wills, Bridget; Flanagan, Aleksandra; Waiyaiya, Emily; Tran, Hai Bac; Cowper, Alison E; Chotiyarnwong, Pojchong; Chotiyarnwon, Pojchong; Grimes, Jonathan M; Yoksan, Sutee; Malasit, Prida; Simmons, Cameron P; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2011-01-01

    The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.

  6. Studies on ADCC (antibody-dependent cell-mediated cytotoxicity) using sheep red blood cells as target cells, 2

    International Nuclear Information System (INIS)

    Ichikawa, Yukinobu; Takaya, Masatoshi; Arimori, Shigeru

    1979-01-01

    A non-specific cytotoxic mediator from effector cells (human peripheral blood leukocytes) was investigated in the ADCC (antibody-dependent cell-mediated cytotoxicity) system using antibody-coated sheep red blood cells (SRBC) as target cells. 51 Cr-labelled homologous (sheep) or heterologous (human) red blood cells were used as adjacent cells. Either crude lymphocyte fraction, phagocyte depleted fraction or granulocyte rich fraction separated from human peripheral leukocytes showed moderate cytotoxic effect on homologous adjacent cells, however no cytotoxic activity on heterologous adjacent cells was demonstrated in any leukocyte fraction. This suggests that the cytotoxic effects on homologous adjacent cells were resulted from the translocation of antibody molecules to adjacent cells from antibody-coated target cells. We concluded that the cytotoxic mechanism in this ADCC system was not mediated by non-specific soluble factors released from either human peripheral lymphocytes, monocytes or granulocytes. (author)

  7. THROMBOCYTOPENIA IN DENGUE HAEMORRHAGIC FEVER

    Directory of Open Access Journals (Sweden)

    I Wayan Putu Sutirta-Yasa

    2013-04-01

    Full Text Available The incidence and geographical distribution of dengue has gradually increased during the past decade. Today, dengue is considered one of the most important arthropod-borne viral diseasases in humans in term of morbidity and mortality. Dengue infection   a potential life-threatening dengue hemorrhagic fever (DHF / dengue shock syndrome(DSS, characterized by thrombocytopenia and increased vascular permiability. Thrombocytopenia causes bleeding, but in   DHF patients with thrombocytopenia do not always develop bleeding manifestation. The pathogenesis of thrombocytopenia are not cleared. Multiple factors  may be involved in the machanisms leading to thrombocytopenia in DHF/DSS patients.

  8. Neurological Manifestations of Dengue Infection

    Directory of Open Access Journals (Sweden)

    Guo-Hong Li

    2017-10-01

    Full Text Available Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS, peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

  9. Health beliefs and practices related to dengue fever: a focus group study.

    Science.gov (United States)

    Wong, Li Ping; AbuBakar, Sazaly

    2013-01-01

    This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16(th) December, 2011 and 12(th) May, 2012. The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments.

  10. Practices of Dengue Fever Prevention and the Associated Factors among the Orang Asli in Peninsular Malaysia.

    Science.gov (United States)

    Chandren, Josephine Rebecca; Wong, Li Ping; AbuBakar, Sazaly

    2015-01-01

    Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia. A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013. A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4%) had a total dengue prevention score of 51-100 (of a possible score of 0-100). Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0-18) were less likely (OR = 0.63, 95%CI = 0.44-0.92 vs. score 19-36, P = 0.015) to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1-5) were more likely (OR = 2.06, 95%CI = 1.21-3.53, vs. score of 6-10, P = 0.008) to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24-0.99, P = 0.045) or rarely fogged (OR = 0.40, 95%CI = 0.22-0.75, P = 0.004) had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1-5) were less likely (OR = 0.54, 95%CI = 0.33-0.89 vs. score of 6-10, P = 0.018) to practice dengue prevention measures. Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli. More outreach on mosquito control campaigns should be carried

  11. Practices of Dengue Fever Prevention and the Associated Factors among the Orang Asli in Peninsular Malaysia.

    Directory of Open Access Journals (Sweden)

    Josephine Rebecca Chandren

    Full Text Available Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia.A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013.A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4% had a total dengue prevention score of 51-100 (of a possible score of 0-100. Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0-18 were less likely (OR = 0.63, 95%CI = 0.44-0.92 vs. score 19-36, P = 0.015 to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1-5 were more likely (OR = 2.06, 95%CI = 1.21-3.53, vs. score of 6-10, P = 0.008 to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24-0.99, P = 0.045 or rarely fogged (OR = 0.40, 95%CI = 0.22-0.75, P = 0.004 had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1-5 were less likely (OR = 0.54, 95%CI = 0.33-0.89 vs. score of 6-10, P = 0.018 to practice dengue prevention measures.Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli. More outreach on mosquito control campaigns should be

  12. Practices of Dengue Fever Prevention and the Associated Factors among the Orang Asli in Peninsular Malaysia

    Science.gov (United States)

    Chandren, Josephine Rebecca; Wong, Li Ping; AbuBakar, Sazaly

    2015-01-01

    Background Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia. Methods A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013. Results A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4%) had a total dengue prevention score of 51–100 (of a possible score of 0–100). Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0–18) were less likely (OR = 0.63, 95%CI = 0.44–0.92 vs. score 19–36, P = 0.015) to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1–5) were more likely (OR = 2.06, 95%CI = 1.21–3.53, vs. score of 6–10, P = 0.008) to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24–0.99, P = 0.045) or rarely fogged (OR = 0.40, 95%CI = 0.22–0.75, P = 0.004) had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1–5) were less likely (OR = 0.54, 95%CI = 0.33–0.89 vs. score of 6–10, P = 0.018) to practice dengue prevention measures. Conclusion Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli

  13. Cells of the J774 macrophage cell line are primed for antibody-dependent cell-mediated cytotoxicity following exposure to γ-irradiation

    International Nuclear Information System (INIS)

    Duerst, R.; Werberig, K.

    1991-01-01

    Activation of macrophages (M phi) for host defense against tumor cells follows a sequence of priming events followed by an initiating stimulus that results in production and release of cytotoxic molecules that mediate target cell killing. The authors have developed a model to study specific macrophage cytotoxicity in vitro utilizing a cultured murine M phi cell line, J774. Specific cytotoxicity of cultured human gastrointestinal tumor cells is achieved in the presence of murine IgG2a monoclonal antibody (mAb) 17-1-A. The ability of these cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) is greatly enhanced following gamma-irradiation. ADCC can be demonstrated at mAb 17-1-A concentrations greater than or equal to 1 microgram/ml and effector/target cell ratios greater than or equal to 2. Exposure to doses greater than or equal to 10 Gy of gamma-irradiation increases ADCC threefold. Varying the duration from J774 M phi exposure to γ-irradiation until addition of antibody-coated target cells showed that the primed state for ADCC is stable for at least 8 days but approximately 24 hr is required for complete development of the primed state. mAb-dependent target cell death begins 8 hr after addition of mAb and labeled target cells to primed effector cells and is complete by 24 hr. Incubation of unirradiated J774 M phi effector cells with recombinant murine interferon-γ (rmIFN-γ) also results in enhanced ADCC, but the extent of target cell killing achieved is less than that following priming by γ-irradiation. Concomitant priming of γ-irradiated J774 M phi with rmIFN-γ increases the extent of ADCC. Further study of irradiated J774 cells may elucidate the molecular pathways utilized by M phi for achieving and maintaining the primed state for ADCC

  14. Lymphocyte antibody-dependent cytotoxicity test for evaluation of clinical role of monoclonal anti-D-antibodies for prevention of rhesus sensitization.

    Science.gov (United States)

    Olovnikova, N I; Belkina, E V; Nikolaeva, T L; Miterev, G Yu; Chertkov, I L

    2006-01-01

    Monoclonal antibodies to D antigen were studied in the reaction of antibody-dependent cytotoxicity for evaluation of the possibility of using these antibodies for preventing rhesus sensitization. High hemolytic activity of four anti-D-monoclonal antibodies in the antibody-dependent cytotoxicity test, mediated by their interaction with FcgammaRI, and the capacity to accelerate elimination of D+ erythrocytes from circulation did not provide the immunosuppressive effect. It was hypothesized that monoclonal antibodies for prevention of rhesus sensitization should interact with FcgammaRIII on lymphocytes. These monoclonal antibodies are extremely rare: only 4 of 125 studied antibodies mediated hemolysis in the antibody-dependent cytotoxicity test with lymphocytes, while all polyclonal anti-D-preparations exhibited this activity.

  15. Introducing dengue vaccine: Implications for diagnosis in dengue vaccinated subjects.

    Science.gov (United States)

    Alagarasu, Kalichamy

    2016-05-27

    Diagnosis of dengue virus infections is complicated by preference for different diagnostic tests in different post onset days of illness and the presence of multiple serotypes leading to secondary and tertiary infections. The sensitivity of the most commonly employed diagnostic assays such as anti dengue IgM capture (MAC) ELISA and non structural protein (NS) 1 capture ELISA are lower in secondary and subsequent infections. Introduction of dengue vaccine in endemic regions will affect the way how dengue is diagnosed in vaccinated subjects. This viewpoint article discusses implications of introduction of dengue vaccine on the diagnosis of dengue infections in vaccinated subjects and the strategies that are needed to tackle the issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. [Dengue, Zika and Chikungunya].

    Science.gov (United States)

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  17. Dengue Fever Treatment

    Science.gov (United States)

    ... AIDS Influenza Malaria Respiratory Syncytial Virus (RSV) Tuberculosis Zika Virus Find a Funding Opportunity Opportunities & Announcements Types of ... For example, the entire genome sequence of the Aedes aegypti mosquito, the main carrier of dengue virus, has been decoded and is available to qualified ...

  18. Autoimmune features caused by dengue fever: a case report

    Directory of Open Access Journals (Sweden)

    Denis Leonardo Fontes Jardim

    Full Text Available Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

  19. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    International Nuclear Information System (INIS)

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made

  20. Dengue fever and dengue haemorrhagic fever in adolescents and adults

    OpenAIRE

    Tantawichien, Terapong

    2012-01-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a...

  1. Generating temporal model using climate variables for the prediction of dengue cases in Subang Jaya, Malaysia

    Science.gov (United States)

    Dom, Nazri Che; Hassan, A Abu; Latif, Z Abd; Ismail, Rodziah

    2013-01-01

    Objective To develop a forecasting model for the incidence of dengue cases in Subang Jaya using time series analysis. Methods The model was performed using the Autoregressive Integrated Moving Average (ARIMA) based on data collected from 2005 to 2010. The fitted model was then used to predict dengue incidence for the year 2010 by extrapolating dengue patterns using three different approaches (i.e. 52, 13 and 4 weeks ahead). Finally cross correlation between dengue incidence and climate variable was computed over a range of lags in order to identify significant variables to be included as external regressor. Results The result of this study revealed that the ARIMA (2,0,0) (0,0,1)52 model developed, closely described the trends of dengue incidence and confirmed the existence of dengue fever cases in Subang Jaya for the year 2005 to 2010. The prediction per period of 4 weeks ahead for ARIMA (2,0,0)(0,0,1)52 was found to be best fit and consistent with the observed dengue incidence based on the training data from 2005 to 2010 (Root Mean Square Error=0.61). The predictive power of ARIMA (2,0,0) (0,0,1)52 is enhanced by the inclusion of climate variables as external regressor to forecast the dengue cases for the year 2010. Conclusions The ARIMA model with weekly variation is a useful tool for disease control and prevention program as it is able to effectively predict the number of dengue cases in Malaysia.

  2. Antibody-dependent cellular cytotoxicity and cytokine/chemokine secretion by KHYG-1 cells stably expressing FcγRIIIA.

    Science.gov (United States)

    Kobayashi, Eiji; Motoi, Sotaro; Sugiura, Masahito; Kajikawa, Masunori; Kojima, Shuji; Kohroki, Junya; Masuho, Yasuhiko

    2014-09-01

    Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is a major mechanism of tumor therapy with antibodies. NK cells not only manifest cytotoxicity but also secrete a variety of cytokines/chemokines that regulate immune responses. Using a retroviral vector, in this study we established a KHYG-1 cell line that stably expresses FcγRIIIA (CD16A). The KHYG-1/FcγRIIIA cells exerted potent antibody concentration-dependent ADCC, whereas parental KHYG-1 cells did not. In contrast, without antibody, the natural killer activity of KHYG-1/FcγRIIIA cells was less potent than that of parental KHYG-1 cells. During the course of ADCC, KHYG-1/FcγRIIIA cells secreted IFN-γ and MIP-1α dependent upon antibody concentration, but parental KHYG-1 cells did not. These results suggest that KHYG-1/FcγRIIIA cells would be useful in studies to elucidate the function of NK cells and the mechanism of ADCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov

    2018-01-01

    The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient a...

  4. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G

    2013-01-01

    to Tn-MUC1 was investigated using BiaCore. The availability of Tn-MUC1 on the surface of breast cancer cells was evaluated by immunohistochemistry, confocal microscopy, and flow cytometry, followed by in vitro assessment of antibody-dependent cellular cytotoxicity by mAb 5E5. Biacore analysis...

  5. Dengue fever: diagnosis and treatment.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2010-07-01

    Dengue fever is a common tropical infection. This acute febrile illness can be a deadly infection in cases of severe manifestation, causing dengue hemorrhagic shock. In this brief article, I will summarize and discuss the diagnosis and treatment of this disease. For diagnosis of dengue, most tropical doctors make use of presumptive diagnosis; however, the definite diagnosis should be based on immunodiagnosis or viral study. Focusing on treatment, symptomatic and supportive treatment is the main therapeutic approach. The role of antiviral drugs in the treatment of dengue fever has been limited, but is currently widely studied.

  6. Overview of current situation of dengue and dengue vector control

    Science.gov (United States)

    Dengue is the most important arbovirus of humans in the world. It is caused by one of four closely related virus serotypes whose primary vector is Aedes aegypti and secondarily by Ae. albopictus. A global dengue pandemic began in Southeast Asia after World War II and has intensified during the las...

  7. Ensemble method for dengue prediction.

    Science.gov (United States)

    Buczak, Anna L; Baugher, Benjamin; Moniz, Linda J; Bagley, Thomas; Babin, Steven M; Guven, Erhan

    2018-01-01

    In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

  8. Ensemble method for dengue prediction.

    Directory of Open Access Journals (Sweden)

    Anna L Buczak

    Full Text Available In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico during four dengue seasons: 1 peak height (i.e., maximum weekly number of cases during a transmission season; 2 peak week (i.e., week in which the maximum weekly number of cases occurred; and 3 total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date.Our approach used ensemble models created by combining three disparate types of component models: 1 two-dimensional Method of Analogues models incorporating both dengue and climate data; 2 additive seasonal Holt-Winters models with and without wavelet smoothing; and 3 simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations.Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week.The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

  9. Micronutrients and Dengue

    OpenAIRE

    Ahmed, Sundus; Finkelstein, Julia L.; Stewart, Anna M.; Kenneth, John; Polhemus, Mark E.; Endy, Timothy P.; Cardenas, Washington; Mehta, Saurabh

    2014-01-01

    Dengue virus infection is the most widespread mosquito-borne viral infection in humans and has emerged as a serious global health challenge. In the absence of effective treatment and vaccine, host factors including nutritional status, which may alter disease progression, need investigation. The interplay between nutrition and other infections is well-established, and modulation of nutritional status often presents a simple low-cost method of interrupting transmission, reducing susceptibility,...

  10. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Science.gov (United States)

    Aguiar, Maíra; Stollenwerk, Nico; Halstead, Scott B

    2016-12-01

    With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only. Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  11. The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

    Directory of Open Access Journals (Sweden)

    Maíra Aguiar

    2016-12-01

    Full Text Available With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia, was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy was noted for children younger than 9 years of age.Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE. An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1 Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2 vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only.Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

  12. Tri-phasic fever in dengue fever.

    Science.gov (United States)

    D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

    2018-04-01

    Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

  13. Dengue antibodies in blood donors.

    Science.gov (United States)

    Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

    2012-01-01

    Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. OBTECTIVE: The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgG(TM)). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed.

  14. Human Immune Response to Dengue Infections

    Science.gov (United States)

    1991-06-30

    had been immunized with yellow fever vaccine and later became infected with dengue 3 virus, responded best to dengue 3 antigen but also responded to...effective dengue virus subunit vaccines . We found evidence of marked T cell activation in patients with DHF. T cell activation in patients with DF was similar...Treatment and Control of Dengue Hemorrhagic Fever. World Health Organization, Geneva, Switzerland 7. Sabin AB (1952) Research on dengue during World

  15. Dengue Disease Risk Mental Models in the City of Dhaka, Bangladesh: Juxtapositions and Gaps Between the Public and Experts.

    Science.gov (United States)

    Dhar-Chowdhury, Parnali; Haque, C Emdad; Driedger, S Michelle

    2016-05-01

    Worldwide, more than 50 million cases of dengue fever are reported every year in at least 124 countries, and it is estimated that approximately 2.5 billion people are at risk for dengue infection. In Bangladesh, the recurrence of dengue has become a growing public health threat. Notably, knowledge and perceptions of dengue disease risk, particularly among the public, are not well understood. Recognizing the importance of assessing risk perception, we adopted a comparative approach to examine a generic methodology to assess diverse sets of beliefs related to dengue disease risk. Our study mapped existing knowledge structures regarding the risk associated with dengue virus, its vector (Aedes mosquitoes), water container use, and human activities in the city of Dhaka, Bangladesh. "Public mental models" were developed from interviews and focus group discussions with diverse community groups; "expert mental models" were formulated based on open-ended discussions with experts in the pertinent fields. A comparative assessment of the public's and experts' knowledge and perception of dengue disease risk has revealed significant gaps in the perception of: (a) disease risk indicators and measurements; (b) disease severity; (c) control of disease spread; and (d) the institutions responsible for intervention. This assessment further identifies misconceptions in public perception regarding: (a) causes of dengue disease; (b) dengue disease symptoms; (c) dengue disease severity; (d) dengue vector ecology; and (e) dengue disease transmission. Based on these results, recommendations are put forward for improving communication of dengue risk and practicing local community engagement and knowledge enhancement in Bangladesh. © 2015 Society for Risk Analysis.

  16. Weather-Driven Variation in Dengue Activity in Australia Examined Using a Process-Based Modeling Approach

    Science.gov (United States)

    Bannister-Tyrrell, Melanie; Williams, Craig; Ritchie, Scott A.; Rau, Gina; Lindesay, Janette; Mercer, Geoff; Harley, David

    2013-01-01

    The impact of weather variation on dengue transmission in Cairns, Australia, was determined by applying a process-based dengue simulation model (DENSiM) that incorporated local meteorologic, entomologic, and demographic data. Analysis showed that inter-annual weather variation is one of the significant determinants of dengue outbreak receptivity. Cross-correlation analyses showed that DENSiM simulated epidemics of similar relative magnitude and timing to those historically recorded in reported dengue cases in Cairns during 1991–2009, (r = 0.372, P < 0.01). The DENSiM model can now be used to study the potential impacts of future climate change on dengue transmission. Understanding the impact of climate variation on the geographic range, seasonality, and magnitude of dengue transmission will enhance development of adaptation strategies to minimize future disease burden in Australia. PMID:23166197

  17. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

    Science.gov (United States)

    Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

    2017-01-01

    The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  18. Tyrosine kinase inhibitors as modulators of trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity in breast cancer cell lines.

    Science.gov (United States)

    Collins, Denis M; Gately, Kathy; Hughes, Clare; Edwards, Connla; Davies, Anthony; Madden, Stephen F; O'Byrne, Kenneth J; O'Donovan, Norma; Crown, John

    2017-09-01

    Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab. Using LDH-release assays, we investigated the impact of antigen modulation, assay duration and peripheral blood mononuclear cell (PBMC) activity on trastuzumab-mediated ADCC in breast cancer models of maximal (SKBR3) and minimal (MCF-7) target antigen expression to determine if modulating the ADCC response to trastuzumab using TKIs may be a viable approach for enhancing tumor immune reactivity. HER2 levels were determined in lapatinib, afatinib and neratinib-treated SKBR3 and MCF-7 using high content analysis (HCA). Trastuzumab-mediated ADCC was assessed following treatment with TKIs utilising a colorimetric LDH release-based protocol at 4 and 12h timepoints. PBMC activity was assessed against non-MHC-restricted K562 cells. A flow cytometry-based method (CFSE/7-AAD) was also used to measure trastuzumab-mediated ADCC in medium-treated SKBR3 and MCF-7. HER2 antigen levels were significantly altered by the three TKIs in both cell line models. The TKIs significantly reduced LDH levels directly in SKBR3 cells but not MCF-7. Lapatinib and neratinib augment trastuzumab-related ADCC in SKBR3 but the effect was not consistent with antigen expression levels and was dependent on volunteer PBMC activity (vs. K562). A 12h assay timepoint produced more consistent results. Trastuzumab-mediated ADCC (PBMC:target cell ratio of 10:1) was measured at 7.6±4.7% (T12) by LDH assay and 19±3.2 % (T12) using the flow cytometry-based method in the antigen-low model MCF-7. In the presence of effector cells with high

  19. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Cortical laminar necrosis in dengue encephalitis-a case report.

    Science.gov (United States)

    Garg, Ravindra Kumar; Rizvi, Imran; Ingole, Rajan; Jain, Amita; Malhotra, Hardeep Singh; Kumar, Neeraj; Batra, Dhruv

    2017-04-20

    Dengue encephalitis is a rare neurological manifestation of dengue fever. Its clinical presentation is similar to other viral encephalitides and encephalopathy. No single specific finding on magnetic resonance imaging of dengue encephalitis has yet been documented. They are highly variable and atypical. A 15-year boy presented with fever, the headache and altered sensorium of 12-day duration. On neurological examination, his Glasgow Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit. Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic resonance imaging of the brain revealed signal changes in bilateral parietooccipital and left frontal regions (left hemisphere more involved than the right hemisphere). There was gyriform enhancement bilateral parietooccipital regions consistent with cortical laminar necrosis. Bilaterally diffuse subcortical white matter was also involved and subtle T2 hyperintensity involving both basal ganglia was noted. Gradient echo sequence revealed presence of hemorrhage in the subcortical white matter. Patient was treated conservatively and received platelet transfusion. Patient became fully conscious after 7 days. In a patient with highly suggestive dengue e\\ephalitis, we describe an unusual magnetic resonance imaging finding. This report is possibly the first instance of cortical laminar necrosis in such a setting.

  1. A critical assessment of vector control for dengue prevention.

    Directory of Open Access Journals (Sweden)

    Nicole L Achee

    2015-05-01

    Full Text Available Recently, the Vaccines to Vaccinate (v2V initiative was reconfigured into the Partnership for Dengue Control (PDC, a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1 a critical assessment of current vector control tools and those under development, (2 outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3 determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations.

  2. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

    Directory of Open Access Journals (Sweden)

    Dewi Marbawati

    2014-08-01

    Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency

  3. Sofosbuvir as treatment against dengue?

    Science.gov (United States)

    Gan, Chye Sheng; Lim, See Khai; Chee, Chin Fei; Yusof, Rohana; Heh, Choon Han

    2018-02-01

    Dengvaxia ® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC 90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue. © 2017 John Wiley & Sons A/S.

  4. Ecg manifestations in dengue infection

    International Nuclear Information System (INIS)

    Tarique, S.; Murtaza, G.; Asif, S.; Qureshi, I.H.

    2013-01-01

    To determine the frequency of ECG changes in patients with dengue fever and dengue hemorrhagic fever. Place of study: Department of Medicine, Mayo Hospital Lahore Duration of study: September to November 201 Study design: Cross sectional analytical study Patient and methods: 116 patients with dengue infection were enrolled in the study. Their clinical presentation and examination was duly noted. Each patient had baseline and then regular monitoring of blood counts, metabolic profile and fluid status. Patients with Dengue Hemorrhagic fever underwent radiological examination in form of chest radiograph and ultrasound abdomen. ECG was carried out in all patients. Results: Out of 116 patients, 61(52.6%) suffered from Dengue Fever and 55(47.4%) had Dengue Hemorrhagic Fever. Overall 78 patients had normal ECG. Abnormal ECG findings like tachycardia, bradycardia, supraventricular tachycardia, left bundle branch block, ST depression, poor progression of R wave were noted. There was no significant relationship of ECG findings with the disease. Conclusion: ECG changes can occur in dengue infection with or without cardiac symptoms. Commonly noted findings were ST depression and bradycardia. (author)

  5. [Current situation and surveillance on dengue fever in China, 2005 - 2007].

    Science.gov (United States)

    Wang, Qin; Xu, Zhen; Dou, Feng-Man; Zhou, Hang; Wang, Xiao-Fang; Yin, Wen-Wu; Li, Qun

    2009-08-01

    To provide scientific evidence for prevention and control program on dengue fever through analyzing the situation of dengue fever in China, from 2005 to 2007. Data was collected from Internet-based National Notifiable Infectious Disease Reporting System, National Enhanced Dengue Fever Surveillance System and field investigation on dengue outbreaks, described and analyzed with descriptively and by SPSS statistical software. There was a total number of 1623 dengue cases (including 1356 laboratory confirmed cases and 267 probable cases) and 1 death case reported in China from 2005 to 2007. Among the identified cases, 151 were imported from foreign countries as the Southeast Asian countries, accounting for 9.3%, while the rest 1472 cases were reported from local infections, identified only in 9 cities from Guangdong and Fujian provinces. Data from the monitoring program on Aedes Mosquitoes indicated that: The indicators of BI from 84.6% of the sentinels were over 5, and BI from 72.2% of the sentinels were over 10. This index was especially at a higher level during summer in the southern areas of China. Aedes albopictus was found in all the sentinel sites while Aedes aegypti was only found in Hainan and in limited counties of Guangdong. No dengue virus was isolated from mosquito vectors collected from national sentinel sites, whereas positive results had been detected by PCR test in Guangdong province. It was assumed that a sustainable local circulation of dengue virus had not yet been established successfully in Mainland China according to the surveillance data. However, more local outbreaks reported in Guangdong and Fujian with the wide distribution and high-level density of aedes mosquito, low antibody level in healthy population and the increasing number of imported dengue cases, there is a potential of Dengue outbreaks in southern China. An integrated mosquito vector monitoring and management system is needed in high risk area to reduce the transmission of dengue

  6. Increased efficiency in the second-hand tire trade provides opportunity for dengue control.

    Science.gov (United States)

    Pliego Pliego, Emilene; Velázquez-Castro, Jorge; Eichhorn, Markus P; Fraguela Collar, Andrés

    2018-01-21

    Dengue fever is increasing in geographical range, spread by invasion of its vector mosquitoes. The trade in second-hand tires has been implicated as a factor in this process because they act as mobile reservoirs of mosquito eggs and larvae. Regional transportation of tires can create linkages between rural areas with dengue and disease-free urban areas, potentially giving rise to outbreaks even in areas with strong local control measures. In this work we sought to model the dynamics of mosquito transportation via the tire trade, in particular to predict its role in causing unexpected dengue outbreaks through vertical transmission of the virus across generations of mosquitoes. We also aimed to identify strategies for regulating the trade in second-hand tires, improving disease control. We created a mathematical model which captures the dynamics of dengue between rural and urban areas, taking into account the movement and storage time of tires, and mosquito diapause. We simulate a series of scenarios in which a mosquito population is introduced to a dengue-free area via movement of tires, either as single or multiple events, increasing the likelihood of a dengue outbreak. A persistent disease state can be induced regardless of whether urban conditions for an outbreak are met, and an existing endemic state can be enhanced by vector input. Finally we assess the potential for regulation of tire processing as a means of reducing the transmission of dengue fever using a specific case study from Puerto Rico. Our work demonstrates the importance of the second-hand tire trade in modulating the spread of dengue fever across regions, in particular its role in introducing dengue to disease-free areas. We propose that reduction of tire storage time and control of their movement can play a crucial role in containing dengue outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Hemoterapia e febre Dengue Blood banking e Dengue fever

    Directory of Open Access Journals (Sweden)

    Estácio F. Ramos

    2008-02-01

    Full Text Available Dengue is an endemic/epidemic arboviral disease with a variable symptomatic benign course, but potentially fatal. Once in an inhabited area, the disease will exist forever, with the best achievement being to keep vectors suppressed and the disease under control. Tiger mosquitoes (aedes aegypti, aedes albopictus are active breeders and urban hunters, becoming resistant to pesticides. Global warming and population growth are propelling the disease worldwide at tropical and subtropical regions, victimizing new populations. Dengue virus is very infective, and has been transmitted by needlestick, intrapartum, through blood transfusion and mucosal contact with blood. One patient got dengue while undergoing bone marrow transplantation. We address the growing dengue epidemics in Brazil, with more than half a million official cases in 2007, to estimate the risks of transfusion transmitted dengue. Calculations however were surpassed by reality: the major Blood Center in Brazil (FHSP-USP has found dengue virus in one out of each thousand blood units. In 2007, industry sold 2,6 million disposable blood bags in Brazil. Plotting data from FHSP-USP to the whole country, 2600 blood units would have been infective. Through blood components, around 5000 patients must have received dengue virus intravenously. Beatty et al. estimated to be 1:1300 the risk for dengue transmission through blood transfusion in Puerto Rico, close to what has been demonstrated in Sao Paulo. Throughout Brazil, the average risk may be lower, but the epidemics grows towards a worst scenario. Whatever the risk is, it imposes that all blood units in Brazil (and wherever dengue is endemic must be EIA tested for dengue NS1 antigen. This marker appears early after infection, and the EIA testing platform is available at all blood banks. Also, donors must report febrile states up to two weeks after donation. Morbidity from dengue virus injected in hospitalized patients is unknown, but it may lead

  8. Appendicular perforation in dengue fever: our experience

    Directory of Open Access Journals (Sweden)

    Gunjan Desai

    2014-09-01

    Full Text Available Dengue viral infections have become one of major emerging infectious diseases in the tropics. Acute abdomen occurring in dengue viral infection is not uncommon. The spectrums of acute surgical emergencies which raise suspicion of an abdominal catastrophe in patients presenting with dengue fever include acute pancreatitis, acute acalculous cholecystitis, non-specific peritonitis and very rarely acute appendicitis. The presence of low white cell count and platelet count can raise suspicion of a diagnosis of dengue in a patient presenting with acute abdominal pain, during a dengue epidemic. We herein report three patients with dengue fever who had appendicular perforation during the course of their viral fever.

  9. Dengue fever and dengue haemorrhagic fever in adolescents and adults.

    Science.gov (United States)

    Tantawichien, Terapong

    2012-05-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients.

  10. Recent advances in understanding dengue

    Science.gov (United States)

    Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

    2016-01-01

    Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research. PMID:26918159

  11. Recent advances in understanding dengue.

    Science.gov (United States)

    Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

    2016-01-01

    Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research.

  12. Dengue viruses – an overview

    Directory of Open Access Journals (Sweden)

    Anne Tuiskunen Bäck

    2013-08-01

    Full Text Available Dengue viruses (DENVs cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF, and dengue shock syndrome (DSS are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  13. Spatial Distribution of Dengue in a Brazilian Urban Slum Setting: Role of Socioeconomic Gradient in Disease Risk.

    Science.gov (United States)

    Kikuti, Mariana; Cunha, Geraldo M; Paploski, Igor A D; Kasper, Amelia M; Silva, Monaise M O; Tavares, Aline S; Cruz, Jaqueline S; Queiroz, Tássia L; Rodrigues, Moreno S; Santana, Perla M; Lima, Helena C A V; Calcagno, Juan; Takahashi, Daniele; Gonçalves, André H O; Araújo, Josélio M G; Gauthier, Kristine; Diuk-Wasser, Maria A; Kitron, Uriel; Ko, Albert I; Reis, Mitermayer G; Ribeiro, Guilherme S

    2015-01-01

    Few studies of dengue have shown group-level associations between demographic, socioeconomic, or geographic characteristics and the spatial distribution of dengue within small urban areas. This study aimed to examine whether specific characteristics of an urban slum community were associated with the risk of dengue disease. From 01/2009 to 12/2010, we conducted enhanced, community-based surveillance in the only public emergency unit in a slum in Salvador, Brazil to identify acute febrile illness (AFI) patients with laboratory evidence of dengue infection. Patient households were geocoded within census tracts (CTs). Demographic, socioeconomic, and geographical data were obtained from the 2010 national census. Associations between CTs characteristics and the spatial risk of both dengue and non-dengue AFI were assessed by Poisson log-normal and conditional auto-regressive models (CAR). We identified 651 (22.0%) dengue cases among 2,962 AFI patients. Estimated risk of symptomatic dengue was 21.3 and 70.2 cases per 10,000 inhabitants in 2009 and 2010, respectively. All the four dengue serotypes were identified, but DENV2 predominated (DENV1: 8.1%; DENV2: 90.7%; DENV3: 0.4%; DENV4: 0.8%). Multivariable CAR regression analysis showed increased dengue risk in CTs with poorer inhabitants (RR: 1.02 for each percent increase in the frequency of families earning ≤1 times the minimum wage; 95% CI: 1.01-1.04), and decreased risk in CTs located farther from the health unit (RR: 0.87 for each 100 meter increase; 95% CI: 0.80-0.94). The same CTs characteristics were also associated with non-dengue AFI risk. This study highlights the large burden of symptomatic dengue on individuals living in urban slums in Brazil. Lower neighborhood socioeconomic status was independently associated with increased risk of dengue, indicating that within slum communities with high levels of absolute poverty, factors associated with the social gradient influence dengue transmission. In addition, poor

  14. Acute disseminated encephalomyelitis in dengue viral infection.

    Science.gov (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The dengue vaccine pipeline: Implications for the future of dengue control

    OpenAIRE

    Schwartz, Lauren M.; Halloran, M. Elizabeth; Durbin, Anna P.; Longini Jr., Ira M.

    2015-01-01

    Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective ...

  16. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

    Directory of Open Access Journals (Sweden)

    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  17. Dengue Virus and Autophagy

    Directory of Open Access Journals (Sweden)

    Nicholas S. Heaton

    2011-08-01

    Full Text Available Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV. Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.

  18. Reviewing dengue: still a neglected tropical disease?

    Science.gov (United States)

    Horstick, Olaf; Tozan, Yesim; Wilder-Smith, Annelies

    2015-04-01

    Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  19. Reviewing dengue: still a neglected tropical disease?

    Directory of Open Access Journals (Sweden)

    Olaf Horstick

    2015-04-01

    Full Text Available Dengue is currently listed as a "neglected tropical disease" (NTD. But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D (2003-2013. NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a poverty related, b endemic to the tropics and subtropics, c lacking public health attention, d having poor research funding and shortcomings in R&D, e usually associated with high morbidity but low mortality, and f often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  20. Dengue fever: a Wikipedia clinical review

    OpenAIRE

    Heilman, James M; Wolff, Jacob De; Beards, Graham M; Basden, Brian J

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treat...

  1. Dengue fever outbreak: a clinical management experience

    International Nuclear Information System (INIS)

    Ahmed, S.; Illyas, M.

    2008-01-01

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107 (2%) presented with typical features of DF, 40/107 (37%) were Dengue-proven while 67/107 (63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-105 degreeC (mean 101 degree C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1 (0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count 40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection, the diagnosis cannot be confirmed unless supported by molecular studies or dengue specific IgM. (author)

  2. Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

    OpenAIRE

    Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-01-01

    Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L...

  3. Human Cytomegalovirus Infection Increases Both Antibody- and Non–Antibody-Dependent Cellular Reactivity by Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Clive M. Michelo, PhD

    2017-12-01

    Conclusions. With regard to organ transplantation, these data suggest that CMV infection enhances NK cell alloreactivity, which may pose an additional adverse effect on graft survival, especially in the presence of donor specific antibodies.

  4. Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection.

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    Thavamalar Balakrishnan

    Full Text Available BACKGROUND: Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4-7 days after fever onset was more than 50% even after primary infection. CONCLUSIONS/SIGNIFICANCE: Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and "innate specificities" seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development.

  5. Dengue virus markers of virulence and pathogenicity

    OpenAIRE

    Rico-Hesse, Rebeca

    2009-01-01

    The increased spread of dengue fever and its more severe form, dengue hemorrhagic fever, have made the study of the mosquito-borne dengue viruses that cause these diseases a public health priority. Little is known about how or why the four different (serotypes 1–4) dengue viruses cause pathology in humans only, and there have been no animal models of disease to date. Therefore, there are no vaccines or antivirals to prevent or treat infection and mortality rates of dengue hemorrhagic fever pa...

  6. Dengue: an arthropod-borne disease of global importance.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Wagenaar, J.; Brandjes, D.P.; Gorp, E. van

    2004-01-01

    Dengue viruses cause a variable spectrum of disease that ranges from an undifferentiated fever to dengue fever to the potentially fatal dengue shock syndrome. Due to the increased incidence and geographical distribution of dengue in the last 50 years, dengue is becoming increasingly recognised as

  7. Occurrence of concurrent infections with multiple serotypes of dengue viruses during 2013–2015 in northern Kerala, India

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    Manchala Nageswar Reddy

    2017-03-01

    Full Text Available Background Dengue is a global human public health threat, causing severe morbidity and mortality. The occurrence of sequential infection by more than one serotype of dengue virus (DENV is a major contributing factor for the induction of Dengue Hemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS, two major medical conditions caused by DENV infection. However, there is no specific drug or vaccine available against dengue infection. There are reports indicating the increased incidence of concurrent infection of dengue in several tropical and subtropical regions. Recently, increasing number of DHF and DSS cases were reported in India indicating potential enhancement of concurrent DENV infections. Therefore, accurate determination of the occurrence of DENV serotype co-infections needs to be conducted in various DENV prone parts of India. In this context, the present study was conducted to analyse the magnitude of concurrent infection in northern Kerala, a southwest state of India, during three consecutive years from 2013 to 2015. Methods A total of 120 serum samples were collected from the suspected dengue patients. The serum samples were diagnosed for the presence of dengue NS1 antigen followed by the isolation of dengue genome from NS1 positive samples. The isolated dengue genome was further subjected to RTPCR based molecular serotyping. The phylogenetic tree was constructed based on the sequence of PCR amplified products. Results Out of the total number of samples collected, 100 samples were positive for dengue specific antigen (NS1 and 26 of them contained the dengue genome. The RTPCR based molecular serotyping of the dengue genome revealed the presence of all four serotypes with different combinations. However, serotypes 1 and 3 were predominant combinations of concurrent infection. Interestingly, there were two samples with all four serotypes concurrently infected in 2013. Discussion All samples containing dengue genome showed the presence of

  8. Cells in Dengue Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  9. Trends in clinical trials of dengue vaccine

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    Priya Marimuthu

    2016-01-01

    Full Text Available Dengue is one of the most important vector-borne disease and an increasing problem worldwide because of current globalization trends. Roughly, half the world′s population lives in dengue endemic countries, and nearly 100 million people are infected annually with dengue. India has the highest burden of the disease with 34% of the global cases. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. There is no licensed dengue vaccine is available still, but several vaccines are under development. Keeping in view the rise in dengue prevalence globally, there is a need to increase clinical drug and vaccine research on dengue. This paper briefly reviews on the development and current status of dengue vaccine to provide information to policymakers, researchers, and public health experts to design and implement appropriate vaccine for prophylactic intervention.

  10. Developing a dengue early warning system using time series model: Case study in Tainan, Taiwan

    Science.gov (United States)

    Chen, Xiao-Wei; Jan, Chyan-Deng; Wang, Ji-Shang

    2017-04-01

    Dengue fever (DF) is a climate-sensitive disease that has been emerging in southern regions of Taiwan over the past few decades, causing a significant health burden to affected areas. This study aims to propose a predictive model to implement an early warning system so as to enhance dengue surveillance and control in Tainan, Taiwan. The Seasonal Autoregressive Integrated Moving Average (SARIMA) model was used herein to forecast dengue cases. Temporal correlation between dengue incidences and climate variables were examined by Pearson correlation analysis and Cross-correlation tests in order to identify key determinants to be included as predictors. The dengue surveillance data between 2000 and 2009, as well as their respective climate variables were then used as inputs for the model. We validated the model by forecasting the number of dengue cases expected to occur each week between January 1, 2010 and December 31, 2015. In addition, we analyzed historical dengue trends and found that 25 cases occurring in one week was a trigger point that often led to a dengue outbreak. This threshold point was combined with the season-based framework put forth by the World Health Organization to create a more accurate epidemic threshold for a Tainan-specific warning system. A Seasonal ARIMA model with the general form: (1,0,5)(1,1,1)52 is identified as the most appropriate model based on lowest AIC, and was proven significant in the prediction of observed dengue cases. Based on the correlation coefficient, Lag-11 maximum 1-hr rainfall (r=0.319, Pclimate variables. Comparing the four multivariate models(i.e.1, 4, 9 and 13 weeks ahead), we found that including the climate variables improves the prediction RMSE as high as 3.24%, 10.39%, 17.96%, 21.81% respectively, in contrast to univariate models. Furthermore, the ability of the four multivariate models to determine whether the epidemic threshold would be exceeded in any given week during the forecasting period of 2010-2015 was

  11. Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

    Science.gov (United States)

    Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

    2016-01-01

    Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

  12. Host genetics and dengue fever.

    Science.gov (United States)

    Xavier-Carvalho, Caroline; Cardoso, Cynthia Chester; de Souza Kehdy, Fernanda; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-12-01

    Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Controlling dengue with vaccines in Thailand.

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    Dennis L Chao

    Full Text Available Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes.We developed an individual-level (including both humans and mosquitoes, stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period.Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.

  14. Climate and dengue transmission: evidence and implications.

    Science.gov (United States)

    Morin, Cory W; Comrie, Andrew C; Ernst, Kacey

    2013-01-01

    Climate influences dengue ecology by affecting vector dynamics, agent development, and mosquito/human interactions. Although these relationships are known, the impact climate change will have on transmission is unclear. Climate-driven statistical and process-based models are being used to refine our knowledge of these relationships and predict the effects of projected climate change on dengue fever occurrence, but results have been inconsistent. We sought to identify major climatic influences on dengue virus ecology and to evaluate the ability of climate-based dengue models to describe associations between climate and dengue, simulate outbreaks, and project the impacts of climate change. We reviewed the evidence for direct and indirect relationships between climate and dengue generated from laboratory studies, field studies, and statistical analyses of associations between vectors, dengue fever incidence, and climate conditions. We assessed the potential contribution of climate-driven, process-based dengue models and provide suggestions to improve their performance. Relationships between climate variables and factors that influence dengue transmission are complex. A climate variable may increase dengue transmission potential through one aspect of the system while simultaneously decreasing transmission potential through another. This complexity may at least partly explain inconsistencies in statistical associations between dengue and climate. Process-based models can account for the complex dynamics but often omit important aspects of dengue ecology, notably virus development and host-species interactions. Synthesizing and applying current knowledge of climatic effects on all aspects of dengue virus ecology will help direct future research and enable better projections of climate change effects on dengue incidence.

  15. Controlling Dengue with Vaccines in Thailand

    Science.gov (United States)

    Chao, Dennis L.; Halstead, Scott B.; Halloran, M. Elizabeth; Longini, Ira M.

    2012-01-01

    Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. Methodology/Principal Findings We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. Conclusions/Significance Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels. PMID:23145197

  16. Health Seeking Behaviour and Treatment Intentions of Dengue and Fever: A Household Survey of Children and Adults in Venezuela

    Science.gov (United States)

    Elsinga, Jelte; Lizarazo, Erley F.; Vincenti, Maria F.; Schmidt, Masja; Velasco-Salas, Zoraida I.; Arias, Luzlexis; Bailey, Ajay; Tami, Adriana

    2015-01-01

    Background Dengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres. Methods Between September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children’s parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals. Results Most individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (ptreating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action. Conclusion Knowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and thereby reduce mortality and severity of dengue. Especially for those with a previous dengue infection, efforts have to be made to promote

  17. Health Seeking Behaviour and Treatment Intentions of Dengue and Fever: A Household Survey of Children and Adults in Venezuela.

    Science.gov (United States)

    Elsinga, Jelte; Lizarazo, Erley F; Vincenti, Maria F; Schmidt, Masja; Velasco-Salas, Zoraida I; Arias, Luzlexis; Bailey, Ajay; Tami, Adriana

    2015-12-01

    Dengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres. Between September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children's parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals. Most individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (p<0.001). Multivariate analysis modelling showed that the independent factors associated with the intention to firstly visit a doctor versus treating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action. Knowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and thereby reduce mortality and severity of

  18. Time series analysis of dengue incidence in Guadeloupe, French West Indies: Forecasting models using climate variables as predictors

    Directory of Open Access Journals (Sweden)

    Ruche Guy

    2011-06-01

    Full Text Available Abstract Background During the last decades, dengue viruses have spread throughout the Americas region, with an increase in the number of severe forms of dengue. The surveillance system in Guadeloupe (French West Indies is currently operational for the detection of early outbreaks of dengue. The goal of the study was to improve this surveillance system by assessing a modelling tool to predict the occurrence of dengue epidemics few months ahead and thus to help an efficient dengue control. Methods The Box-Jenkins approach allowed us to fit a Seasonal Autoregressive Integrated Moving Average (SARIMA model of dengue incidence from 2000 to 2006 using clinical suspected cases. Then, this model was used for calculating dengue incidence for the year 2007 compared with observed data, using three different approaches: 1 year-ahead, 3 months-ahead and 1 month-ahead. Finally, we assessed the impact of meteorological variables (rainfall, temperature and relative humidity on the prediction of dengue incidence and outbreaks, incorporating them in the model fitting the best. Results The 3 months-ahead approach was the most appropriate for an effective and operational public health response, and the most accurate (Root Mean Square Error, RMSE = 0.85. Relative humidity at lag-7 weeks, minimum temperature at lag-5 weeks and average temperature at lag-11 weeks were variables the most positively correlated to dengue incidence in Guadeloupe, meanwhile rainfall was not. The predictive power of SARIMA models was enhanced by the inclusion of climatic variables as external regressors to forecast the year 2007. Temperature significantly affected the model for better dengue incidence forecasting (p-value = 0.03 for minimum temperature lag-5, p-value = 0.02 for average temperature lag-11 but not humidity. Minimum temperature at lag-5 weeks was the best climatic variable for predicting dengue outbreaks (RMSE = 0.72. Conclusion Temperature improves dengue outbreaks forecasts

  19. Is drought helping or killing dengue? Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2015-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  20. Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition.

    Science.gov (United States)

    Blackall, Douglas P; Pesek, Gina D; Montgomery, Matthew M; Oza, Krishna K; Arndt, Patricia A; Garratty, George; Shahcheraghi, Ali; Denomme, Gregory A

    2008-10-01

    The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies against these antigens are uncommon, and there have been only rare case reports of hemolytic disease of the fetus and newborn due to anti-Ge. In this case report, we present a neonate with severe anemia and hyperbilirubinemia due to anti-Ge3. Routine and special laboratory studies undertaken in this case suggested two mechanisms for the patient's hemolysis and persistent anemia. Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia, anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell growth was associated with late anemia and normal bilirubin and reticulocyte values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected neonates may require intensive initial therapy and close follow-up for at least several weeks after delivery.

  1. Could peak proteinuria determine whether patient with dengue fever develop dengue hemorrhagic/dengue shock syndrome? - A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Suhail Sufi M

    2011-08-01

    Full Text Available Abstract Background Worldwide there is a need to develop simple effective predictors that can distinguish whether a patient will progress from dengue fever (DF to life threatening dengue hemorrhagic (DHF or dengue shock syndrome (DSS. We explored whether proteinuria could be used as such a marker. Methods We included patients admitted to hospital with suspected dengue fever. Starting at enrollment until discharge, each patient's daily spot urine protein creatinine ratio (UPCR was measured. We classified those with confirmed dengue infection as DF or DHF (including DSS based on WHO criteria. Peak and day of onset of proteinuria was compared between both groups. Results Compared to those with DF, patients with DHF had significantly higher median peak proteinuria levels (0.56 versus 0.08 g/day; p Conclusions Peak UPCR could potentially predict DHF in patients with dengue requiring close monitoring and treatment.

  2. Impedimetric Dengue Biosensor based on Functionalized Graphene Oxide Wrapped Silica Particles

    International Nuclear Information System (INIS)

    Jin, Seon-Ah; Poudyal, Shishir; Marinero, Ernesto E.; Kuhn, Richard J.; Stanciu, Lia A.

    2016-01-01

    Highlights: • 3D graphene oxide based material design. • Fabrication of a label-free dengue DNA and RNA impedimetric biosensor. • Design of a surface-based dengue sensor with good selectivity and detection limit. - Abstract: A composite of 3-Aminopropyltriethoxysilane (APTES) functionalized graphene oxide (APTES-GO) wrapped on SiO 2 particles (SiO 2 @APTES-GO) was prepared via self-assembly. Transmission electron microscopy (TEM) and ATR-Fourier Transform Infrared spectroscopy (ATR-FTIR) confirmed wrapping of the SiO 2 particles by the APTES-GO sheets. An impedimetric biosensor was constructed and used to sensitively detect dengue DNA and dengue RNA via primer hybridization using different oligonucleotide sequences. The results demonstrated that the SiO 2 @APTES-GO electrode material led to enhanced dengue RNA detection sensitivity with selectivity and detection limit (1 femto-Molar), compared to both APTES-GO and APTES-SiO 2 . The three-dimensional structure, higher contact area, electrical properties and the ability for rapid hybridization offered by the SiO 2 @APTES-GO led to the successful design of a dengue biosensor with the lowest detection limit reported to date.

  3. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

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    Wen-Yang Tsai

    2017-07-01

    Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  4. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue

    OpenAIRE

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algori...

  5. Clinical and laboratory profile of different dengue sub types in dengue virus infection

    OpenAIRE

    Niloy Gan Chaudhuri; S. Vithyavathi; K. Sankar

    2016-01-01

    Background: Dengue infection, an arthropod-borne viral hemorrhagic fever is caused by Arbovirus of Flavivirus genus and transmitted by Aedes aegypti, Aedes albopictus. Liver involvement in dengue fever is manifested by the elevation of transaminases representing reactive hepatitis, due to direct attack of virus itself or the use of hepatotoxic drugs. The objective of the study was to investigate clinical and laboratory profile of different dengue sub type's patients admitted for dengue fever....

  6. Current management of severe dengue infection.

    Science.gov (United States)

    Lee, Tau Hong; Lee, Linda Kay; Lye, David Chien; Leo, Yee Sin

    2017-01-01

    Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.

  7. Hemophagocytic syndrome in classic dengue fever

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    Sayantan Ray

    2011-01-01

    Full Text Available A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnostic criteria of the HLH 2004 protocol of the Histiocyte Society. The patient recovered with corticosteroid therapy. A review of literature revealed only a handful of case reports that showed the evidence that this syndrome is caused by dengue virus. Our patient is an interesting case of hemophagocytic syndrome associated with classic dengue fever and contributes an additional case to the existing literature on this topic. This case highlights the need for increased awareness even in infections not typically associated with hemophagocytic syndrome.

  8. Post encephalitic parkinsonism following dengue viral infection

    OpenAIRE

    Bopeththa, B. V. K. M.; Ralapanawa, U.

    2017-01-01

    Background Incidence of dengue fever as well as dengue hemorrhagic fever is increasing in Sri Lanka especially among elderly population. As the number of cases is rising, rare complications of dengue illness also can be seen in clinical practice when compared to the past few years. Prompt identification and treatment of such complications is challenging due to lack of awareness and unavailability of standard treatment. Case presentation 69 years old man presented with acute onset fever and wa...

  9. CLINICAL AND LABORATORY PROFILE OF DENGUE FEVER

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    Farhan Fazal

    2015-02-01

    Full Text Available AIM: Dengue is a major health problem in many parts of India and Gulbarga (North Karnataka was previously not a known endemic area f or dengue. Infection with dengue virus can cause a spectrum of three clinical syndromes , classic dengue fever (DF , dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The present study was undertaken to determine the disease profile of dengue virus infection in hospitalized patients. METHODS AND MATERIAL: One hundred patients admitted in Basaveshwar Teaching and General hospital with fever more than 38.5 degree Celsius and IgM dengue positive were selected. They were followed from the onset of fever to twelve days or till they are recovered according to WHO discharge criteria whichever is earlier. They underwent relevant investigations to identify specific organ dysfunction and categorize them into the spectrum of Dengue fever in accordance to W HO criteria . RESULTS: Out of 100 cases in this study 70 cases belongs to DF , 23 cases to DHF and 7 cases to DSS based on WHO criteria. All the cases had fever (100%. Other common symptoms noted were myalgia (61% , joint pain (54% , headache (66% , vomitin g (55% , pain abdomen (48% , rash (41% , hepatomegaly (20% , bleeding (21% and shock (8%. Hess test was positive in 24% patients. Low platelet count of less than 100 , 000/cu mm according to WHO criteria was present in 73% patients. Deranged liver functio n test and renal parameters were seen in 26 and 8 patients respectively . Mortality documented was 7 patients due to delayed presentation. The average duration of hospital stay was 4.65 days. CONCLUSION: Dengue fever was a more common manifestation than DHF or DSS. During aepidemic , dengue should be strongly considered on the differential diagnosis of any patient with fever. The treatment of dengue is mainly fluid management and supportive. Early recognition and management of alarm symptoms is the key to bet ter outcome

  10. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B; Russell, Philip K

    2016-03-29

    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.

    Science.gov (United States)

    Scott, Lesley J

    2016-09-01

    Tetravalent, live-attenuated, dengue vaccine (Dengvaxia(®); CYD-TDV) is the first vaccine approved for the prevention of dengue disease caused by dengue virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high dengue endemic areas. This narrative review discusses the immunogenicity, protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of dengue disease. In Latin American and Asian phase 3 trials in children and adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was efficacious in preventing virologically-confirmed dengue (VCD) during the period from 28 days after the last dose (month 13) to month 25, meeting the primary endpoint criteria. Protective efficacy against VCD in the respective individual trials was 60.8 and 56.5 % (primary analysis). During the 25-month active surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in children aged 9 years and older. CYD-TDV was generally well tolerated, with no safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1) in ongoing long-term studies. Based on evidence from the dengue clinical trial program, the WHO SAGE recommended that countries with high dengue endemicity consider introducing CYD-TDV as part of an integrated disease prevention strategy to lower disease burden. Pharmacoeconomic considerations will be pivotal to implementing dengue vaccination prevention strategies in these countries. The availability of a dengue vaccine is considered essential if the 2012 WHO global strategy targets for reducing the burden of dengue disease by 2020 are to be attained. Hence, CYD-TDV represents a major advance for the prevention of dengue disease in high dengue endemic regions.

  12. Economic Cost of Dengue in Puerto Rico

    Science.gov (United States)

    Halasa, Yara A.; Shepard, Donald S.; Zeng, Wu

    2012-01-01

    Dengue, endemic in Puerto Rico, reached a record high in 2010. To inform policy makers, we derived annual economic cost. We assessed direct and indirect costs of hospitalized and ambulatory dengue illness in 2010 dollars through surveillance data and interviews with 100 laboratory-confirmed dengue patients treated in 2008–2010. We corrected for underreporting by using setting-specific expansion factors. Work absenteeism because of a dengue episode exceeded the absenteeism for an episode of influenza or acute otitis media. From 2002 to 2010, the aggregate annual cost of dengue illness averaged $38.7 million, of which 70% was for adults (age 15+ years). Hospitalized patients accounted for 63% of the cost of dengue illness, and fatal cases represented an additional 17%. Households funded 48% of dengue illness cost, the government funded 24%, insurance funded 22%, and employers funded 7%. Including dengue surveillance and vector control activities, the overall annual cost of dengue was $46.45 million ($12.47 per capita). PMID:22556069

  13. Dengue fever outbreak: a clinical management experience.

    Science.gov (United States)

    Ahmed, Shahid; Ali, Nadir; Ashraf, Shahzad; Ilyas, Mohammad; Tariq, Waheed-Uz-Zaman; Chotani, Rashid A

    2008-01-01

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. An observational study. The Combined Military Hospital, Malir Cantt., Karachi, from August 2005 to December 2006. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107(2%) presented with typical features of DF, 40/107(37%) were Dengue-proven while 67/107(63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-1050C (mean 1010C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1(0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection; the diagnosis cannot be confirmed unless supported by

  14. Chloroquine use improves dengue-related symptoms

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    Marcos Carvalho Borges

    2013-08-01

    Full Text Available Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63% with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004 while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.

  15. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  16. P. vivax malaria and dengue fever co-infection: a cross-sectional study in the Brazilian Amazon.

    Directory of Open Access Journals (Sweden)

    Belisa M L Magalhães

    2014-10-01

    Full Text Available Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity.A cross-sectional study was conducted (2009 to 2011 in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1% presented P. vivax malaria mono-infection, 584 (37% dengue fever mono-infection, and 44 (2.8% were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected, deep bleeding (vs. P. vivax mono-infected, hepatomegaly, and jaundice (vs. dengue mono-infected.In endemic areas for dengue and malaria, jaundice (in dengue patients and spontaneous bleeding (in malaria patients should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group.

  17. P. vivax Malaria and Dengue Fever Co-infection: A Cross-Sectional Study in the Brazilian Amazon

    Science.gov (United States)

    Magalhães, Belisa M. L.; Siqueira, André M.; Alexandre, Márcia A. A.; Souza, Marcela S.; Gimaque, João B.; Bastos, Michele S.; Figueiredo, Regina M. P.; Melo, Gisely C.; Lacerda, Marcus V. G.; Mourão, Maria P. G.

    2014-01-01

    Background Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity. Methodology/Principal Findings A cross-sectional study was conducted (2009 to 2011) in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1%) presented P. vivax malaria mono-infection, 584 (37%) dengue fever mono-infection, and 44 (2.8%) were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected), deep bleeding (vs. P. vivax mono-infected), hepatomegaly, and jaundice (vs. dengue mono-infected). Conclusions/Significance In endemic areas for dengue and malaria, jaundice (in dengue patients) and spontaneous bleeding (in malaria patients) should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group. PMID:25340346

  18. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue.

    Science.gov (United States)

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algorithm to prioritize FDA-approved drugs from dengue-related diseases to treat dengue. When tested in a de-novo validation setting, DenguePredict found the only two drugs tested in clinical trials for treating dengue and ranked them highly: chloroquine ranked at top 0.96% and ivermectin at top 22.75%. We showed that drugs targeting immune systems and arachidonic acid metabolism-related apoptotic pathways might represent innovative drugs to treat dengue. In summary, DenguePredict, by combining comprehensive disease- and drug-related data and novel algorithms, may greatly facilitate drug discovery for dengue.

  19. Dengue related maculopathy and foveolitis.

    Science.gov (United States)

    Juanarita, Jaafar; Azmi, Mohd Noor Raja; Azhany, Yaakub; Liza-Sharmini, Ahmad Tajudin

    2012-09-01

    A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.

  20. Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

    Science.gov (United States)

    Bialuk, Izabela; Whitney, Stephen; Andresen, Vibeke; Florese, Ruth H; Nacsa, Janos; Cecchinato, Valentina; Valeri, Valerio W; Heraud, Jean-Michel; Gordon, Shari; Parks, Robyn Washington; Montefiori, David C; Venzon, David; Demberg, Thorsten; Guroff, Marjorie Robert-; Landucci, Gary; Forthal, Donald N; Franchini, Genoveffa

    2011-12-09

    The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. Published by Elsevier Ltd.

  1. Blood banking e Dengue fever

    OpenAIRE

    Ramos, Estácio F.

    2008-01-01

    Dengue is an endemic/epidemic arboviral disease with a variable symptomatic benign course, but potentially fatal. Once in an inhabited area, the disease will exist forever, with the best achievement being to keep vectors suppressed and the disease under control. Tiger mosquitoes (aedes aegypti, aedes albopictus) are active breeders and urban hunters, becoming resistant to pesticides. Global warming and population growth are propelling the disease worldwide at tropical and subtropical regions,...

  2. Clinical profile and outcome of Dengue fever cases.

    Science.gov (United States)

    Ratageri, Vinod H; Shepur, T A; Wari, P K; Chavan, S C; Mujahid, I B; Yergolkar, P N

    2005-08-01

    Dengue fever is on rise globally. In India, Dengue epidemics are expanding geographically, even into the rural areas. Dengue can present with varied manifestations. The mortality rate has been brought down with high index of suspicion, strict monitoring and proper fluid resuscitation. Herewith, we are presenting clinical features and outcome of Dengue cases seen in and around Hubli (North Karnataka).

  3. A model of dengue fever

    Directory of Open Access Journals (Sweden)

    Boutayeb A

    2003-02-01

    Full Text Available Abstract Background Dengue is a disease which is now endemic in more than 100 countries of Africa, America, Asia and the Western Pacific. It is transmitted to the man by mosquitoes (Aedes and exists in two forms: Dengue Fever and Dengue Haemorrhagic Fever. The disease can be contracted by one of the four different viruses. Moreover, immunity is acquired only to the serotype contracted and a contact with a second serotype becomes more dangerous. Methods The present paper deals with a succession of two epidemics caused by two different viruses. The dynamics of the disease is studied by a compartmental model involving ordinary differential equations for the human and the mosquito populations. Results Stability of the equilibrium points is given and a simulation is carried out with different values of the parameters. The epidemic dynamics is discussed and illustration is given by figures for different values of the parameters. Conclusion The proposed model allows for better understanding of the disease dynamics. Environment and vaccination strategies are discussed especially in the case of the succession of two epidemics with two different viruses.

  4. Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Amol Hartalkar

    2015-08-01

    Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

  5. Spatio-temporal modelling of climate-sensitive disease risk: Towards an early warning system for dengue in Brazil

    Science.gov (United States)

    Lowe, Rachel; Bailey, Trevor C.; Stephenson, David B.; Graham, Richard J.; Coelho, Caio A. S.; Sá Carvalho, Marilia; Barcellos, Christovam

    2011-03-01

    This paper considers the potential for using seasonal climate forecasts in developing an early warning system for dengue fever epidemics in Brazil. In the first instance, a generalised linear model (GLM) is used to select climate and other covariates which are both readily available and prove significant in prediction of confirmed monthly dengue cases based on data collected across the whole of Brazil for the period January 2001 to December 2008 at the microregion level (typically consisting of one large city and several smaller municipalities). The covariates explored include temperature and precipitation data on a 2.5°×2.5° longitude-latitude grid with time lags relevant to dengue transmission, an El Niño Southern Oscillation index and other relevant socio-economic and environmental variables. A negative binomial model formulation is adopted in this model selection to allow for extra-Poisson variation (overdispersion) in the observed dengue counts caused by unknown/unobserved confounding factors and possible correlations in these effects in both time and space. Subsequently, the selected global model is refined in the context of the South East region of Brazil, where dengue predominates, by reverting to a Poisson framework and explicitly modelling the overdispersion through a combination of unstructured and spatio-temporal structured random effects. The resulting spatio-temporal hierarchical model (or GLMM—generalised linear mixed model) is implemented via a Bayesian framework using Markov Chain Monte Carlo (MCMC). Dengue predictions are found to be enhanced both spatially and temporally when using the GLMM and the Bayesian framework allows posterior predictive distributions for dengue cases to be derived, which can be useful for developing a dengue alert system. Using this model, we conclude that seasonal climate forecasts could have potential value in helping to predict dengue incidence months in advance of an epidemic in South East Brazil.

  6. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    Science.gov (United States)

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  7. Neurological manifestations of dengue viral infection

    Directory of Open Access Journals (Sweden)

    Carod-Artal FJ

    2014-10-01

    Full Text Available Francisco Javier Carod-Artal1,21Neurology Department, Raigmore hospital, Inverness, UK; 2Universitat Internacional de Catalunya (UIC, Barcelona, Spain Abstract: Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%–7.4% of symptomatic cases. Neurological complications have been classified into dengue virus encephalopathy, dengue virus encephalitis, immune-mediated syndromes (acute disseminated encephalomyelitis, myelitis, Guillain–Barré syndrome, neuritis brachialis, acute cerebellitis, and others, neuromuscular complications (hypokalemic paralysis, transient benign muscle dysfunction and myositis, and dengue-associated stroke. Common neuro-ophthalmic complications are maculopathy and retinal vasculopathy. Pathogenic mechanisms include systemic complications and metabolic disturbances resulting in encephalopathy, direct effect of the virus provoking encephalitis, and postinfectious immune mechanisms causing immune-mediated syndromes. Dengue viruses should be considered as a cause of neurological disorders in endemic regions. Standardized case definitions for specific neurological complications are still needed. Keywords: encephalitis, encephalopathy, dengue fever, neurological complications

  8. Social justice, climate change, and dengue.

    Science.gov (United States)

    Chang, Aileen Y; Fuller, Douglas O; Carrasquillo, Olveen; Beier, John C

    2014-06-14

    Climate change should be viewed fundamentally as an issue of global justice. Understanding the complex interplay of climatic and socioeconomic trends is imperative to protect human health and lessen the burden of diseases such as dengue fever. Dengue fever is rapidly expanding globally. Temperature, rainfall, and frequency of natural disasters, as well as non-climatic trends involving population growth and migration, urbanization, and international trade and travel, are expected to increase the prevalence of mosquito breeding sites, mosquito survival, the speed of mosquito reproduction, the speed of viral incubation, the distribution of dengue virus and its vectors, human migration patterns towards urban areas, and displacement after natural disasters. The burden of dengue disproportionately affects the poor due to increased environmental risk and decreased health care. Mobilization of social institutions is needed to improve the structural inequalities of poverty that predispose the poor to increased dengue fever infection and worse outcomes. This paper reviews the link between dengue and climatic factors as a starting point to developing a comprehensive understanding of how climate change affects dengue risk and how institutions can address the issues of social justice and dengue outbreaks that increasingly affect vulnerable urban populations. Copyright © 2014 Chang, Fuller, Carrasquillo, Beier. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  9. Dengue and Chikungunya Vector Control Pocket Guide

    Science.gov (United States)

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  10. Host cell responses to dengue virus infection

    NARCIS (Netherlands)

    Diosa Toro, Mayra

    2017-01-01

    Dengue (ook wel knokkelkoorts) is de meest voorkomende virale infectieziekte dat wordt overgedragen door muggen in de wereld met naar schatting 390 miljoen infecties per jaar. Ondanks de grote klinische impact en economische schade van het dengue virus is er nog steeds geen behandeling beschikbaar.

  11. [Hepatic alterations in patients with dengue].

    Science.gov (United States)

    Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

    2005-06-01

    Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

  12. Recent Advances in Dengue: Relevance to Puerto Rico

    Science.gov (United States)

    Noyd, David H.; Sharp, Tyler M.

    2015-01-01

    Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012–2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals’ ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico. PMID:26061055

  13. Simultaneous development of antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity in irradiated mice reconstituted with bone marrow cells

    International Nuclear Information System (INIS)

    Sihvola, M.; Hurme, M.

    1987-01-01

    Spleen cells from irradiated, bone marrow-reconstituted mice were tested for their ability to mediate antibody-dependent cellular cytotoxicity against P815 target (ADCC-P815), ADCC against sheep red blood cells (ADCC-SRBC), and natural killer (NK) activity judged as YAC-1 lysis at different times after bone marrow reconstitution. Donor-derived ADCC-P815 effectors were found to appear in the spleens 10-12 days after bone marrow reconstitution simultaneously with the appearance of donor-derived NK cells. NK cells recently derived from bone marrow are known to express the Thy-1 antigen; the phenotype of the ''early'' ADCC-P815 effectors was found to be the same as that of NK cells, i.e., Thy-1+, asialo-GM1+. These data suggest that ADCC-P815 effector cells belong to the NK cell population. ADCC-SRBC, in contrast to ADCC-P815 and NK activity, was already high on Day 7 after bone marrow reconstitution. However, it was mediated partly by recipient-derived effectors. ADCC-SRBC effectors were characterized to be different from ADCC-P815 effectors

  14. Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.

    Science.gov (United States)

    Kato, Yukinari; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Uchida, Hiroaki; Tahara, Hideaki; Yamada, Shinji; Yanaka, Miyuki; Nakamura, Takuro; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Honma, Ryusuke; Takagi, Michiaki; Ogasawara, Satoshi; Murata, Takeshi; Kaneko, Mika K

    2017-02-01

    The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG 2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

  15. Reduced antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells of salivary polymorphonuclear leukocytes and inhibition of peripheral blood polymorphonuclear leukocyte cytotoxicity by saliva.

    Science.gov (United States)

    Ashkenazi, M; Kohl, S

    1990-06-15

    Blood polymorphonuclear leukocytes (BPMN) have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) against HSV-infected cells. Although HSV infections are frequently found in the oral cavity, the ADCC capacity of salivary PMN (SPMN) has not been studied, mainly because methods to isolate SPMN were not available. We have recently developed a method to isolate SPMN, and in this study have evaluated their ADCC activity against HSV-infected cells. SPMN were obtained by repeated washings of the oral cavity, and separated from epithelial cells by nylon mesh filtration. ADCC was quantitatively determined by 51Cr release from HSV-infected Chang liver cells. SPMN in the presence of antibody were able to destroy HSV-infected cells, but SPMN were much less effective in mediating ADCC than BPMN (3.4% vs 40.7%, p less than 0.0001). In the presence of antiviral antibody, SPMN were able to adhere to HSV-infected cells, but less so than BPMN (34% vs 67%), and specific antibody-induced adherence was significantly lower in SPMN (p less than 0.04). The spontaneous adherence to HSV-infected cells was higher for SPMN than BPMN. SPMN demonstrated up-regulation of the adhesion glycoprotein CD18, but down-regulation of the FcRIII receptor. Incubation with saliva decreased ADCC capacity of BPMN, up-regulated CD18 expression, and down-regulated FcRIII expression.

  16. Re-emergence of dengue virus serotype 2 strains in the 2013 outbreak in Nepal

    Science.gov (United States)

    Gupta, Birendra Prasad; Singh, Sneha; Kurmi, Roshan; Malla, Rajani; Sreekumar, Easwaran; Manandhar, Krishna Das

    2015-01-01

    Background & objectives: Epidemiological interventions and mosquito control are the available measures for dengue control. The former approach uses serotype and genetic information on the circulating virus strains. Dengue has been frequently reported from Nepal, but this information is mostly lacking. The present study was done to generate a comprehensive clinical and virological picture of a dengue outbreak in Nepal during 2013. Methods: A hospital-based study involving patients from five districts of Nepal was carried out. Demographic information, clinical details and dengue serological status were obtained. Viral RNA was characterized at the molecular level by reverse-transcription polymerase chain reaction (RT-PCR), nucleotide sequencing and phylogenetic analysis. Results: From among the 2340 laboratory-confirmed dengue cases during the study period, 198 patients consented for the study. Clinically they had fever (100%), headache (59.1%), rashes (18.2%), retro-orbital pain (30.3%), vomiting (15.1%), joint pain (28.8%) and thrombocytopenia (74.3%). Fifteen (7.5%) of them had mucosal bleeding manifestations, and the rest were uncomplicated dengue fever. The patients were mostly adults with a mean age of 45.75 ± 38.61 yr. Of the 52 acute serum samples tested, 15 were positive in RT-PCR. The causative virus was identified as DENV serotype 2 belonging to the Cosmopolitan genotype. Interpretations & conclusions: We report here the involvement of DENV serotype 2 in an outbreak in Nepal in 2013. Earlier outbreaks in the region in 2010 were attributed to serotype 1 virus. As serotype shifts are frequently associated with secondary infections and severe disease, there is a need for enhancing surveillance especially in the monsoon and post-monsoon periods to prevent large-scale, severe dengue outbreaks in the region. PMID:26905233

  17. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  18. Dengue fever: a Wikipedia clinical review.

    Science.gov (United States)

    Heilman, James M; De Wolff, Jacob; Beards, Graham M; Basden, Brian J

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.

  19. Knowledge and practice regarding dengue and chikungunya

    DEFF Research Database (Denmark)

    Kajeguka, Debora C; Desrochers, Rachelle E; Mwangi, Rose

    2017-01-01

    OBJECTIVE: To investigate knowledge and prevention practices regarding dengue and chikungunya amongst community members, as well as knowledge, treatment and diagnostic practices among healthcare workers. METHOD: We conducted a cross-sectional survey with 125 community members and 125 healthcare...... good knowledge. We conducted qualitative survey (n = 40) to further assess knowledge and practice regarding dengue and chikungunya fever. RESULTS: 15.2% (n = 19) of community members had good knowledge regarding dengue, whereas 53.6%, (n = 67) of healthcare workers did. 20.3% (n = 16) of participants...... from lowland areas and 6.5% (n = 3) from highland areas had good knowledge of dengue (χ(2) = 4.25, P = 0.03). Only 2.4% (n = 3) of all participants had a good knowledge score for chikungunya. In the qualitative study, community members expressed uncertainty about dengue and chikungunya. Some healthcare...

  20. Transmission spectroscopy of dengue viral infection

    International Nuclear Information System (INIS)

    Firdous, S; Ahmed, M; Rehman, A; Nawaz, M; Anwar, S; Murtaza, S

    2012-01-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 – 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 – 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 – 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients

  1. Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

    Science.gov (United States)

    Villamor, E; Villar, L A; Lozano, A; Herrera, V M; Herrán, O F

    2017-10-01

    Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

  2. Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

    OpenAIRE

    Anna P. Durbin; Stephen S. Whitehead

    2011-01-01

    Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Past...

  3. Ongoing dengue epidemic - Angola, June 2013.

    Science.gov (United States)

    2013-06-21

    On April 1, 2013, the Public Health Directorate of Angola announced that six cases of dengue had been reported to the Ministry of Health of Angola (MHA). As of May 31, a total of 517 suspected dengue cases had been reported and tested for dengue with a rapid diagnostic test (RDT). A total of 313 (60.5%) specimens tested positive for dengue, including one from a patient who died. All suspected cases were reported from Luanda Province, except for two from Malanje Province. Confirmatory diagnostic testing of 49 specimens (43 RDT-positive and six RDT-negative) at the CDC Dengue Branch confirmed dengue virus (DENV) infection in 100% of the RDT-positive specimens and 50% of the RDT-negative specimens. Only DENV-1 was detected by molecular diagnostic testing. Phylogenetic analysis indicated this virus has been circulating in the region since at least 1968, strongly suggesting that dengue is endemic in Angola. Health-care professionals throughout Angola should be aware of the ongoing epidemic, the recommended practices for clinical management of dengue patients, and the need to report cases to MHA. Persons in Angola should seek medical care for acute febrile illness to reduce the risk for developing complications. Laboratory-confirmed dengue also has been reported from seven countries on four continents among persons who had recently traveled to Luanda, including 79 persons from Portugal. Angola is the third of four African countries to report a dengue outbreak in 2013. Persons returning from Africa with acute febrile illness should seek medical care, including testing for DENV infection, and suspected cases should be reported to public health authorities.

  4. Dengue encephalitis with predominant cerebellar involvement: Report of eight cases with MR and CT imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Hegde, Vinay; Bhat, Maya; Prasad, Chandrajit; Gupta, A.K.; Saini, Jitender [National Institute of Mental Health and Neurosciences, Department of Neuroimaging and Interventional Radiology, Bangalore, Karnataka (India); Aziz, Zarina [Sri Sathya Sai Institute of Medical Science, Department of Radiology, Bangalore (India); Kumar, Sharath [Apollo Hospital, Department of Neuroradiology, Bangalore (India); Netravathi, M. [National Institute of Mental Health and Neurosciences, Department of Neurology, Bangalore (India)

    2014-11-01

    CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. (orig.)

  5. Dengue encephalitis with predominant cerebellar involvement: Report of eight cases with MR and CT imaging features

    International Nuclear Information System (INIS)

    Hegde, Vinay; Bhat, Maya; Prasad, Chandrajit; Gupta, A.K.; Saini, Jitender; Aziz, Zarina; Kumar, Sharath; Netravathi, M.

    2015-01-01

    CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. (orig.)

  6. PATHOGENESIS OF HEMORRHAGIC DUE TO DENGUE VIRUS

    Directory of Open Access Journals (Sweden)

    Arief Suseno

    2015-01-01

    Full Text Available Dengue is a viral disease that is mediated by a mosquito, which causes morbidity and mortality. Viruses can increase vascular permeability which can lead to hemorrhagic diathesis or disseminated intravascular coagulation (DIC known as dengue hemorrhagic fever (DHF. In Indonesia, dengue hemorrhagic fever (DHF are caused by dengue virus infection which was found to be endemic accompanied by an explosion of extraordinary events that appear at various specified period. The diagnosis of dengue is determined based on the criteria of the World Health Organization (WHO, 1999, which are sudden high fever accompanied by a marked tendency to hemorrhage positive tourniquet test, petechiae, ecchymosis, purpura, mucosal hemorrhagic, hematemesis or melena and thrombocytopenia. The problem that still exists today is the mechanism of thrombocytopenia in patients with varying degrees of dengue involving levels of vWF (von Willebrand factor and prostaglandin I2 (PGI2 can not be explained. The mechanism of hemorrhagic in dengue virus infections acquired as a result of thrombocytopenia, platelet disfunction decreased coagulation factors, vasculopathy with endothelial injury and disseminated intravascular coagulation (DIC.

  7. Dengue situation in Brazil by year 2000

    Directory of Open Access Journals (Sweden)

    Hermann G Schatzmayr

    2000-01-01

    Full Text Available Dengue virus types 1 and 2 have been isolated in Brazil by the Department of Virology, Instituto Oswaldo Cruz, in 1986 and 1990 respectively, after many decades of absence. A successful continental Aedes aegypti control program in the Americas, has been able to eradicate the vector in most countries in the 60's, but the program could not be sustained along the years. Dengue viruses were reintroduced in the American region and the infection became endemic in Brazil, like in most Central and SouthAmerican countries and in the Caribbean region, due to the weaning of the vector control programs in these countries. High demographic densities and poor housing conditions in large urban communities, made the ideal conditions for vector spreading. All four dengue types are circulating in the continent and there is a high risk of the introduction in the country of the other two dengue types in Brazil, with the development of large epidemics. After the Cuban episode in 1981, when by the first time a large epidemic of dengue hemorrhagic fever and dengue shock syndrome have been described in the Americas, both clinical presentations are observed, specially in the countries like Brazil, with circulation of more than one dengue virus type. A tetravalent potent vaccine seems to be the only possible way to control the disease in the future, besides rapid clinical and laboratory diagnosis, in order to offer supportive treatment to the more severe clinical infections.

  8. A PATIENT DENGUE HEMORRHAGIC FEVER WITH SPASMS

    Directory of Open Access Journals (Sweden)

    Ulfa Kholili

    2014-09-01

    Full Text Available Indonesia is one of the countries with the high endemic of Dengue viral infection followed by Thailand, Myanmar, India and Srilanka. For more 10-15 years, Dengue Viral Infection/DHF has become a cause of patient who should be hospitalized and was the first cause of death children in south easthern Asia.1,2 Batavia was the first city of Indonesia found Dengue Viral infection which had been written in journal by David Bylon in the 1779. Encephalopathy of dengue (ED is one unusually complication of dengue viral infection which had been characterized by aberration the arrangement of nerves central (CNS. This paper want to describe of a young teenage with suffer from DHF and seizure. Beside it, pleural effusion and cerebral edema had been found. Seizure most likely due to dengue encephalopathy associated with cerebral edema and was supported by positive IgG and IgM anti dengue. Corticosteroid was given to improve cerebral edema. By good management as long as admission, she was discharged from hospital with a good condition.

  9. Dengue: a new challenge for neurology

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    2012-11-01

    Full Text Available Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world’s population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial.

  10. DengueTools: innovative tools and strategies for the surveillance and control of dengue

    Directory of Open Access Journals (Sweden)

    Annelies Wilder-Smith

    2012-03-01

    Full Text Available Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of ‘Comprehensive control of Dengue fever under changing climatic conditions’. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named ‘DengueTools’ to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas: Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring. Research area 2: Develop novel strategies to prevent dengue in children. Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of ‘DengueTools’. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant

  11. DengueTools: innovative tools and strategies for the surveillance and control of dengue.

    Science.gov (United States)

    Wilder-Smith, Annelies; Renhorn, Karl-Erik; Tissera, Hasitha; Abu Bakar, Sazaly; Alphey, Luke; Kittayapong, Pattamaporn; Lindsay, Steve; Logan, James; Hatz, Christoph; Reiter, Paul; Rocklöv, Joacim; Byass, Peter; Louis, Valérie R; Tozan, Yesim; Massad, Eduardo; Tenorio, Antonio; Lagneau, Christophe; L'Ambert, Grégory; Brooks, David; Wegerdt, Johannah; Gubler, Duane

    2012-01-01

    Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of 'Comprehensive control of Dengue fever under changing climatic conditions'. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named 'DengueTools' to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas:Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring.Research area 2: Develop novel strategies to prevent dengue in children.Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of 'DengueTools'. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589 Dengue Tools.

  12. Environmental and Socio-Demographic Determinants of Dengue Fever in Colombo City, Sri Lanka

    Science.gov (United States)

    Tipre, Meghan; Luvall, Jeffrey; Haque, Akhlaque; McClure, Leslie; Zaitchik, Ben; Sathiakumar, Nalini

    2014-01-01

    Dengue fever has increased exponentially in Sri Lanka, from 24.4 cases per 100,000 in 2003 to 165.3 per 100,000 population in 2013. Although early warning systems using predictor models have been previously developed in other settings, it is important to develop such models in each local setting. Further, the ability of these models to be applicable at smaller geographic units will enhance current vector control and disease surveillance measures. The aim of this paper was to identify environmental and socio-economic status (SES) risk factors that may predict dengue fever at the Gram Niladhari Divisions (GND) level (smallest administrative unit) in Colombo city, Sri Lanka. These factors included landcover classes, amount of vegetation, population density, water access and neighborhood SES as determined by roof type. A geographically weighted regression (GWR) was used to develop the prediction model. A total 55 GND units covering an area of 37 sq km were investigated. We found that GND units with decreased vegetation, higher built-up area, higher population density and poor access to tap-water supply were associated with high risk of dengue; the pertinent GND units were concentrated in the center of the city. This is the first study in Sri Lanka to include both environmental and socio-demographic factors in prediction models for dengue fever. The methodology may be useful in enhancing ongoing dengue fever control measures in the country, and to be extended to other countries in the region that have an increasing incidence of dengue fever.

  13. Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model.

    Science.gov (United States)

    Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Stewart-Jones, Guillaume; Scarlatti, Gabriella; Fomsgaard, Anders

    2017-11-17

    The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKR CCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1 subtypes. The immunogen inducing the most potent and broadest ADCC response was a trimeric gp140. The ADCC activity was highest against the HIV-1 subtype corresponding to the immunogen. The ADCC activity did not necessarily reflect neutralizing activity in the pseudovirus-TZMbl assay, but there was an overall correlation between the two antiviral activities. We present a rabbit vaccination model and an assay suitable for screening HIV-1 vaccine candidates for the induction of ADCC-mediating antibodies in addition to neutralizing antibodies. The antigens and/or immunization strategies capable of inducing antibodies with ADCC activity did not necessarily induce neutralizing activity and vice versa. Nevertheless, we identified vaccine candidates that were able to concurrently induce both types of responses and that had ADCC activity that was cross-reactive between different subtypes. When searching for an effective vaccine candidate, it is important to evaluate the antibody response using a model and an assay measuring the desired function.

  14. Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Abe, Shinji; Nishioka, Yasuhiko; Kunita, Akiko; Fukayama, Masashi; Fujii, Yuki; Ogasawara, Satoshi; Kato, Yukinari

    2017-04-01

    Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology. In this study we developed chLpMab-2, a human-mouse chimeric anti-hPDPN antibody, derived from LpMab-2. chLpMab-2 was produced using fucosyltransferase 8-knockout (KO) Chinese hamster ovary (CHO)-S cell lines. By flow cytometry, chLpMab-2 reacted with hPDPN-expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab-2 exhibited high antibody-dependent cellular cytotoxicity (ADCC) against PDPN-expressing cells, despite its low complement-dependent cytotoxicity. Furthermore, treatment with chLpMab-2 abolished tumor growth in xenograft models of CHO/hPDPN, indicating that chLpMab-2 suppressed tumor development via ADCC. In conclusion, chLpMab-2 could be useful as a novel antibody-based therapy against hPDPN-expressing tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity.

    Science.gov (United States)

    Kaneko, Mika K; Nakamura, Takuro; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Yamada, Shinji; Yanaka, Miyuki; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Ogasawara, Satoshi; Kato, Yukinari

    2017-06-01

    Podoplanin is expressed in many cancers, including oral cancers and brain tumors. The interaction between podoplanin and its receptor C-type lectin-like receptor 2 (CLEC-2) has been reported to be involved in cancer metastasis and tumor malignancy. We previously established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23 (IgG 1 , kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab. However, we have not shown the usefulness of LpMab-23 for antibody therapy against podoplanin-expressing cancers. In this study, we first determined the minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23 (chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab-23 showed high sensitivity against a podoplanin-expressing glioblastoma cell line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using human natural killer cells, indicating that chLpMab-23 could be useful for antibody therapy against podoplanin-expressing cancers.

  16. The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection.

    Science.gov (United States)

    Rajalingam, Raja

    2016-01-01

    Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  17. The impact of HLA class I-specific killer cell immunoglobulin-like receptors on antibody-dependent natural killer cell-mediated cytotoxicity and organ allograft rejection

    Directory of Open Access Journals (Sweden)

    Raja Rajalingam

    2016-12-01

    Full Text Available Natural killer (NK cells of the innate immune system are cytotoxic lymphocytes that play important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self HLA class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIR is involved in the calibration of NK cell effector capacities during a developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self HLA class I (due to virus infection or tumor transformation or HLA class I disparities (in the setting of allogeneic transplantation. NK cells expressing an inhibitory KIR binding self HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC, triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  18. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Jamil, T.; Mehmood, K.; Mujtaba, G.; Choudhry, N.

    2012-01-01

    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  19. Lo que usted debe saber acerca del dengue

    OpenAIRE

    Vélez, Juan David; Fundación Valle de Lili; Salazar, Juan Carlos; Rosso Suárez, Fernando

    1998-01-01

    Epidemiología del dengue/Transmisión/Presentación clínica/Síntomas en niños/Diagnostico de laboratorio/Dengue clásico/Dengue hemorrágico/Dengue hemorrágico con choque/ ¿Qué es dengue hemorrágico?/ ¿Cuál es la diferencia entre dengue hemorrágico y dengue clásico?/ ¿Qué son las plaquetas?/ ¿Qué puedo hacer para prevenir el dengue?/ ¿Cuándo debo consultar?/ ¿Cuándo se debe hacer un hemograma?/ ¿Cuándo se debe hospitalizar un paciente con dengue?

  20. Dengue Haemorrhagic Fever presenting as Acute Abdomen

    OpenAIRE

    Al-Araimi, Hanaa; Al-Jabri, Amal; Mehmoud, Arshad; Al-Abri, Seif

    2011-01-01

    We describe a case of a 38 year-old Sri Lankan female who was referred to the surgeon on call with a picture of acute abdomen. She presented with a three-day history of fever, headache, abdominal pain and diarrhoea; however, the physical examination was not consistent with acute abdomen. Her platelet count was 22 ×109/L. A diagnosis of dengue haemorrhagic fever (DHF) was made and dengue serology was positive. Dengue epidemics have been associated with a variety of gastrointestinal symptoms an...

  1. Transmission Dinamics Model Of Dengue Fever

    Science.gov (United States)

    Debora; Rendy; Rahmi

    2018-01-01

    Dengue fever is an endemic disease that is transmitted through the Aedes aegypti mosquito vector. The disease is present in more than 100 countries in America, Africa, and Asia, especially tropical countries. Differential equations can be used to represent the spread of dengue virus occurring in time intervals and model in the form of mathematical models. The mathematical model in this study tries to represent the spread of dengue fever based on the data obtained and the assumptions used. The mathematical model used is a mathematical model consisting of Susceptible (S), Infected (I), Viruses (V) subpopulations. The SIV mathematical model is then analyzed to see the solution behaviour of the system.

  2. Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

    Science.gov (United States)

    Wong, Jacklyn; Stoddard, Steven T.; Astete, Helvio; Morrison, Amy C.; Scott, Thomas W.

    2011-01-01

    Background Because no dengue vaccine or antiviral therapy is commercially available, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Traditional models of Ae. aegypti assume that population dynamics are regulated by density-dependent larval competition for food and little affected by oviposition behavior. Due to direct impacts on offspring survival and development, however, mosquito choice in oviposition site can have important consequences for population regulation that should be taken into account when designing vector control programs. Methodology/Principal Findings We examined oviposition patterns by Ae. aegypti among 591 naturally occurring containers and a set of experimental containers in Iquitos, Peru. Using larval starvation bioassays as an indirect measure of container food content, we assessed whether females select containers with the most food for their offspring. Our data indicate that choice of egg-laying site is influenced by conspecific larvae and pupae, container fill method, container size, lid, and sun exposure. Although larval food positively influenced oviposition, our results did not support the hypothesis that females act primarily to maximize food for larvae. Females were most strongly attracted to sites containing immature conspecifics, even when potential competitors for their progeny were present in abundance. Conclusion/Significance Due to strong conspecific attraction, egg-laying behavior may contribute more to regulating Ae. aegypti populations than previously thought. If highly infested containers are targeted for removal or larvicide application, females that would have preferentially oviposited in those sites may instead distribute their eggs among other suitable, previously unoccupied containers. Strategies that kill mosquitoes late in their development (i.e., insect growth regulators that kill pupae rather than larvae) will enhance vector control by creating

  3. Profile of dengue hepatitis in children from India and its correlation with WHO dengue case classifiation

    Directory of Open Access Journals (Sweden)

    Neelam Mohan

    2017-06-01

    Full Text Available Objective: To study the profile of liver involvement in children with dengue fever and to compare the severity of liver involvement with World Health Organization case definition. Methods: A prospective study was carried out from October 2013 to December 2014. Serologically confirmed dengue patients were grouped into three categories according to the World Health Organization classification. Groups 1 and 2 were dengue fever without and with warning signs, respectively; Group 3 was severe dengue. Biochemical and clinical profile of hepatic involvement was studied. Results: A total of 162 children with dengue fever (M:F = 2.37 were included in the study. Median (inter quartile range age was 12 years (IQR: 0.5–18 years. Hepatitis was observed in 151 (93.2% patients. Analysis revealed that out of all liver function test parameters, total bilirubin was found to be a significant predictor of dengue category two and three and albumin and ALT levels were significant predictors for category three. Eight cases presented with ALF. Their median AST was 4 817 (range 61–26 957; median ALT was 2 386 (range 39–11 100; median INR was 2.57 (range 1.6–4.2 and their median serum bilirubin was 2.95 (range 0.6–9.0. Conclusions: Some degree of hepatitis is very common in dengue infection with rise in AST being more than ALT irrespective of the severity of dengue. Severity of hepatitis correlates well with the severity of dengue and can help in triaging of dengue patients. Of all liver function parameters, total bilirubin levels correlate best with severity of dengue infection.

  4. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  5. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  6. Economic value of dengue vaccine in Thailand.

    Science.gov (United States)

    Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

    2011-05-01

    With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

  7. Dengue e dengue hemorrágico: aspectos do manejo na unidade de terapia intensiva Dengue and dengue hemorrhagic fever: management issues in an intensive care unit

    Directory of Open Access Journals (Sweden)

    Sunit Singhi

    2007-05-01

    Full Text Available OBJETIVOS: Descrever a epidemiologia, as características clínicas e o tratamento do dengue e das síndromes do choque associadas ao dengue. FONTES DOS DADOS: Para esta revisão de literatura, foi feita uma pesquisa no Pubmed e nos websites da Organização Mundial da Saúde (OMS e OPAS usando os termos dengue e síndrome do choque associada ao dengue. A informação foi complementada com a experiência pessoal dos autores. SÍNTESE DOS DADOS: O dengue é a mais importante doença viral transmitida por artrópodos em seres humanos. A doença se manifesta de diversas formas, variando desde uma síndrome viral não-diferenciada até febre hemorrágica e choque grave. O dengue é uma enfermidade autolimitada, não específica, caracterizada por febre, cefaléia, mialgia, e sintomas constitucionais. As formas mais graves (febre hemorrágica e síndrome do choque podem levar a um comprometimento multissistêmico e ao óbito. O diagnóstico precoce e um acompanhamento contínuo do agravamento e da resposta ao tratamento são necessários em todos os casos. A OMS recomenda uma abordagem escalonada para o manejo, adequada para as formas mais leves e para o choque precoce. Nas formas mais graves, é preciso uma abordagem agressiva de reanimação com fluidos e de suporte à falência de órgãos em pacientes em estado crítico. As pesquisas sobre as diferenças fisiopatológicas entre o choque do dengue e o choque séptico, seleção de fluidos, agentes inotrópicos e técnicas de suporte a órgãos podem beneficiar os pacientes em estado crítico. CONCLUSÕES: Não há uma terapia específica para infecções causadas pelo dengue. Um bom tratamento de suporte pode salvar vidas mas, em última análise, as iniciativas de controle do vetor e de prevenção contra picadas do mosquito podem trazer os maiores benefícios.OBJECTIVES: To describe the epidemiology, clinical features and treatment of dengue fever and dengue shock syndrome. SOURCES: To prepare

  8. Dengue: an update on treatment options.

    Science.gov (United States)

    Chan, Candice Y Y; Ooi, Eng Eong

    2015-01-01

    Dengue is the most important mosquito-borne viral pathogen globally, with approximately 100 million cases of acute dengue annually. Infection can result in severe, life-threatening disease. Currently, there is no effective vaccine or licensed antiviral. Management is primarily supportive with fluids. Direct antiviral therapies that reduce dengue severity could be useful although these would need to inhibit all four viral serotypes effectively. This review focuses on the interventions that currently considered the gold standard in case management as well as exploratory therapies that have been studied in clinical trials. Although antiviral drug and therapeutic antibodies for dengue remain a work in progress, these studies have produced some promising results and may have the potential to be future drugs.

  9. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  10. Dengue Fever in the United States

    Centers for Disease Control (CDC) Podcasts

    Dr. Amesh Adalja, an associate at the Center for Biosecurity and clinical assistant professor at the University of Pittsburgh School, of Medicine, discusses dengue fever outbreaks in the United States.

  11. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    Science.gov (United States)

    1980-01-01

    1973). Sabin (1948) showed that attenuated dpngiie, passed through mosquitoes, did not revert to pathogenicity frnr man. -7- Thus even if the vaccine ...AD-A138 518 PATHOGENESIS OF DENGUE VACCINE YIRUSES IN MOSQUITOES 1/ (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 9i JAN 80 DRND7...34 ’ UNCLASSIFIED 0{) AD 0Pathogenesis of dengue vaccine viruses in mosquitoes -First Annual Report Barry I. Beaty, Ph.D. Thomas H. G

  12. A Rapporteur's Summary : Research on Dengue Vaccine

    OpenAIRE

    Kitamura, Takashi

    1994-01-01

    Dengue virus is a member of flavivirus group. Diseases caused by flaviviruses have been a scourge of mankind for long history of human kind; with yellow fever at the top, followed by dengue fever, Japanese encephalitis (JE) and Russian spring-summer encephalitis (RSSE). Due to the dvevelopment of a safe and efficacious live-attenuated vaccine against yellow fever as a first laboratory-designed virus vaccine, this disease is no longer a threat in countries where adequate vaccination is practic...

  13. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Henrique Horta Veloso

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  14. Acute atrial fibrillation during dengue hemorrhagic fever

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    Veloso Henrique Horta

    2003-01-01

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  15. An expanded dengue syndrome patient with manifestation myocarditis: case report

    Science.gov (United States)

    Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

    2018-03-01

    Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

  16. Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.

    Science.gov (United States)

    Itai, Shunsuke; Ohishi, Tomokazu; Kaneko, Mika K; Yamada, Shinji; Abe, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Ohba, Shun-Ichi; Nishioka, Yasuhiko; Kawada, Manabu; Harada, Hiroyuki; Kato, Yukinari

    2018-04-27

    Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG 1 , kappa). Herein, we engineered PcMab-47 into 47-mG 2a , a mouse IgG 2a -type mAb, to add antibody-dependent cellular cytotoxicity (ADCC). We further developed 47-mG 2a -f, a core fucose-deficient type of 47-mG 2a to augment its ADCC. Immunohistochemical analysis of oral cancer tissues using PcMab-47 and 47-mG 2a revealed that the latter stained oral squamous cell carcinoma (OSCC) cells in a cytoplasmic pattern at a much lower concentration. PcMab-47 and 47-mG 2a detected PODXL in 163/201 (81.1%) and in 197/201 (98.0%) OSCC samples, respectively. 47-mG 2a -f also detected PODXL in OSCCs at a similar frequency as 47-mG 2a . In vitro analysis revealed that both 47-mG 2a and 47-mG 2a -f exhibited strong complement-dependent cytotoxicity (CDC) against CHO/hPODXL cells. In contrast, 47-mG 2a -f exhibited much stronger ADCC than 47-mG 2a against OSCC cells, indicating that ADCC and CDC of those anti-PODXL mAbs depend on target cells. In vivo analysis revealed that both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in CHO/hPODXL xenograft models at a dose of 100 μg or 500 μg/mouse/week administered twice. 47-mG 2a -f, but not 47-mG 2a , exerted antitumor activity in SAS and HSC-2 xenograft models at a dose of 100 μg/mouse/week administered three times. Although both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in HSC-2 xenograft models at a dose of 500 μg/mouse/week administered twice, 47-mG 2a -f also showed higher antitumor activity than 47-mG 2a . These results suggested that a core fucose-deficient anti-PODXL mAb could be useful for antibody-based therapy against PODXL-expressing OSCCs.

  17. A potential therapy for chordoma via antibody-dependent cell-mediated cytotoxicity employing NK or high-affinity NK cells in combination with cetuximab.

    Science.gov (United States)

    Fujii, Rika; Schlom, Jeffrey; Hodge, James W

    2018-05-01

    OBJECTIVE Chordoma is a rare bone tumor derived from the notochord and is resistant to conventional therapies such as chemotherapy, radiotherapy, and targeting therapeutics. Expression of epidermal growth factor receptor (EGFR) in a large proportion of chordoma specimens indicates a potential target for therapeutic intervention. In this study the authors investigated the potential role of the anti-EGFR antibody cetuximab in immunotherapy for chordoma. METHODS Since cetuximab is a monoclonal antibody of the IgG1 isotype, it has the potential to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) employing natural killer (NK) cells as effectors. Polymorphisms in the CD16 allele expressed on NK cells have been shown to influence the degree of ADCC of tumor cells, with the high-affinity valine (V)/V allele being responsible for more lysis than the V/phenylalanine (F) or FF allele. Unfortunately, however, only approximately 10% of the population expresses the VV allele on NK cells. An NK cell line, NK-92, has now been engineered to endogenously express IL-2 and the high-affinity CD16 allele. These irradiated high-affinity (ha)NK cells were analyzed for lysis of chordoma cells with and without cetuximab, and the levels of lysis observed in ADCC were compared with those of NK cells from donors expressing the VV, VF, and FF alleles. RESULTS Here the authors demonstrate for the first time 1) that cetuximab in combination with NK cells can mediate ADCC of chordoma cells; 2) the influence of the NK CD16 polymorphism in cetuximab-mediated ADCC for chordoma cell lysis; 3) that engineered haNK cells-that is, cells transduced to express the CD16 V158 FcγRIIIa receptor-bind cetuximab with similar affinity to normal NK cells expressing the high-affinity VV allele; and 4) that irradiated haNK cells induce ADCC with cetuximab in chordoma cells. CONCLUSIONS These studies provide rationale for the use of cetuximab in combination with irradiated haNK cells for therapy for

  18. A forecasting model for dengue incidence in the District of Gampaha, Sri Lanka.

    Science.gov (United States)

    Withanage, Gayan P; Viswakula, Sameera D; Nilmini Silva Gunawardena, Y I; Hapugoda, Menaka D

    2018-04-24

    Dengue is one of the major health problems in Sri Lanka causing an enormous social and economic burden to the country. An accurate early warning system can enhance the efficiency of preventive measures. The aim of the study was to develop and validate a simple accurate forecasting model for the District of Gampaha, Sri Lanka. Three time-series regression models were developed using monthly rainfall, rainy days, temperature, humidity, wind speed and retrospective dengue incidences over the period January 2012 to November 2015 for the District of Gampaha, Sri Lanka. Various lag times were analyzed to identify optimum forecasting periods including interactions of multiple lags. The models were validated using epidemiological data from December 2015 to November 2017. Prepared models were compared based on Akaike's information criterion, Bayesian information criterion and residual analysis. The selected model forecasted correctly with mean absolute errors of 0.07 and 0.22, and root mean squared errors of 0.09 and 0.28, for training and validation periods, respectively. There were no dengue epidemics observed in the district during the training period and nine outbreaks occurred during the forecasting period. The proposed model captured five outbreaks and correctly rejected 14 within the testing period of 24 months. The Pierce skill score of the model was 0.49, with a receiver operating characteristic of 86% and 92% sensitivity. The developed weather based forecasting model allows warnings of impending dengue outbreaks and epidemics in advance of one month with high accuracy. Depending upon climatic factors, the previous month's dengue cases had a significant effect on the dengue incidences of the current month. The simple, precise and understandable forecasting model developed could be used to manage limited public health resources effectively for patient management, vector surveillance and intervention programmes in the district.

  19. Wolbachia and dengue virus infection in the mosquito Aedes fluviatilis (Diptera: Culicidae.

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    Jéssica Barreto Lopes Silva

    Full Text Available Dengue represents a serious threat to human health, with billions of people living at risk of the disease. Wolbachia pipientis is a bacterial endosymbiont common to many insect species. Wolbachia transinfections in mosquito disease vectors have great value for disease control given the bacterium's ability to spread into wild mosquito populations, and to interfere with infections of pathogens, such as dengue virus. Aedes fluviatilis is a mosquito with a widespread distribution in Latin America, but its status as a dengue vector has not been clarified. Ae. fluviatilis is also naturally infected by the wFlu Wolbachia strain, which has been demonstrated to enhance infection with the avian malarial parasite Plasmodium gallinaceum. We performed experimental infections of Ae. fluviatilis with DENV-2 and DENV-3 isolates from Brazil via injection or oral feeding to provide insight into its competence for the virus. We also examined the effect of the native Wolbachia infection on the virus using a mosquito line where the wFlu infection had been cleared by antibiotic treatment. Through RT-qPCR, we observed that Ae. fluviatilis could become infected with both viruses via either method of infection, although at a lower rate than Aedes aegypti, the primary dengue vector. We then detected DENV-2 and DENV-3 in the saliva of injected mosquitoes, and observed that injection of DENV-3-infected saliva produced subsequent infections in naïve Ae. aegypti. However, across our data we observed no difference in prevalence of infection and viral load between Wolbachia-infected and -uninfected mosquitoes, suggesting that there is no effect of wFlu on dengue virus. Our results highlight that Ae. fluviatilis could potentially serve as a dengue vector under the right circumstances, although further testing is required to determine if this occurs in the field.

  20. Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmission.

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    Louis Lambrechts

    2010-05-01

    Full Text Available The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses, including the most prevalent arboviral pathogen of humans, dengue virus (DENV. Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from "natural experiments" indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic

  1. Pediatric ischemic stroke due to dengue vasculitis.

    Science.gov (United States)

    Nanda, Subrat Kumar; Jayalakshmi, Sita; Mohandas, Surath

    2014-10-01

    Dengue infection is an important arboviral infection in southeast Asia, especially in India. Neurological manifestations of dengue are increasingly recognized. We report an ischemic stroke due to dengue vasculitis in an 8-year-old child. We present a girl with a short febrile illness followed by episodic severe headache, with gradually progressive hemiparesis and visual impairment. Her brain magnetic resonance imaging revealed multiple infarctions in the anterior and posterior circulation. The magnetic resonance angiogram revealed irregular narrowing of bilateral middle cerebral arteries, right anterior cerebral artery, left posterior cerebral, and bilateral vertebral arteries suggestive of vasculitis. Her dengue serology was strongly positive for immunoglobulin M with 68.9 panbio units. The rest of the evaluation for pediatric stroke was unremarkable. She was treated with intravenous followed by oral corticosteroids and recovered totally with resolution of vasculitis on magnetic resonance angiogram over the next 3 months. This child illustrates possible immune-mediated vasculitis caused by dengue infection which is rather a rare presentation in a child who subsequently recovered well. One should consider dengue in childhood strokes in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The effects of urban growth on dengue

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    Marco Aurélio Pereira Horta

    2014-09-01

    Full Text Available Objective: To analyze the spatial and temporal dynamics of dengue in Coronel Fabriciano, Minas Gerais State, Brazil, and to associate cases to the growth of urban areas and loss of natural areas in recent years. Methods: This is a descriptive, exploratory study, with a quantitative approach. Dengue cases of 2009 were obtained from the Health Municipal Secretariat, including the suspected and confirmed cases. Shape files were obtained, containing information about the municipal boundary, boundary of the urban area, census tracts, areas with buildings and natural areas. Based on the distribution of dengue cases, the Kernel estimator was used to measure data dispersion. Results: Dengue cases reported were georeferenced in GIS (Geographic Information System environment. The landscape showed changes in the units of urban area and pasture, as an urban growth over the pasture matrix. No changes were observed in the areas of remaining forest and eucalyptus. There are cases spatially spread with a tendency to form clusters. Conclusion: Cases of dengue were observed spatially clustered in the northern region of the city, where new neighborhoods have emerged in recent years, following the population growth without proper structure of urbanization and urban planning. In addition, urban growth have reduced the margin of watercourses providing a bare soil, suitable for accumulation of trash and formation of breeding sites for mosquitoes. Efficient public policies and appropriate urban planning might reduce the impact of dengue in endemic regions. doi: http://dx.doi.org/10.5020/18061230.2013.p539

  3. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  4. Dengue mortality in Colombia, 1985-2012.

    Science.gov (United States)

    Chaparro-Narváez, Pablo; León-Quevedo, Willian; Castañeda-Orjuela, Carlos Andrés

    2016-02-11

    Dengue in Colombia is an important public health problem due to the huge economic and social costs it has caused, especially during the disease outbreaks.  To describe the behavior of dengue mortality in Colombia between 1985 and 2012.  We conducted a descriptive study. Information was obtained from mortality and population projection databases provided by the Departamento Administrativo Nacional de Estadística (DANE) for the 1985-2012 period. Mortality rates, rate ratios, and case fatality rates were estimated.  A total of 1,990 dengue deaths were registered during this period in Colombia. Dengue mortality rates presented an increasing trend with statistical significance between 1985 and 1998. Higher mortality rates were reported in men both younger than 5 years and older than 65 years. Between 1995 and 2012, category 1 to 4 municipalities reported the highest mortality rates. Case fatality rates varied during the period between 0.01% and 0.39%.  Dengue is an avoidable disease that should disappear from mortality statistics as a cause of death. The event is avoidable if the proposed activities from the Estrategia de Gestión Integrada (EGI)-Dengue are implemented and evaluated. We recommend encouraging the development of an informational culture to contribute to decision making and prioritizing resource allocation.

  5. Facing dengue fever - our first experience

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    Cvjetković Dejan

    2017-01-01

    Full Text Available Introduction. Dengue fever is a mosquito-borne disease caused by dengue virus, endemic in tropical and subtropical regions, where it is mostly imported from. The most common clinical form is classic dengue fever. We presented the first dengue case microbiologically confirmed in Serbia. Case report. A 34-year-old male got classic dengue fever after arrival from Cuba. The disease occurred suddenly with fever, myalgias, skin rash, hepatosplenomegaly, cytopenia, abnormal aminotransferase and creatine kinase levels. The diagnosis was confirmed with virological diagnostic methods. Significant leukopenia and thrombocytopenia as well as elevation of serum creatine kinase activity were recorded from the very beginning of hospitalization, but were gradually normalized. The whole duration of hospitalization was accompanied by laboratory signs of liver lesion. The disease had favourable outcome. At hospital discharge, the patient was afebrile, asymptomatic, with discrete erythematous rash on torso and arms, normal hemathological values and creatine kinase level and moderately elevated alanine-aminotransferase level. Conclusion. Considering global climate changes and growing international traffic, our health care service needs to be ready for possible massive outbreaks of dengue and other tropical infectious diseases in forthcoming years.

  6. Seropositivity of Dengue Antibodies during Pregnancy

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    Nor Azlin Mohamed Ismail

    2014-01-01

    Full Text Available Purpose. Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM during pregnancy and its neonatal transmission in dengue seropositive women. Methods. Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM using an enzyme-linked immunosorbent assay (ELISA. Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive Care Unit (NICU were analyzed. Results. Out of 358 women recruited, about 128 (35.8% patients were seropositive. Twelve patients (3.4% had recent infections (IgM positive and another 116 women (32.4% were with past infections (IgG positive. All babies born to seropositive mothers had positive IgG paired cord blood; however, no IgM seropositivity was observed. All neonates had good Apgar scores and did not require NICU admission. Conclusion. In this study, 35.8% pregnant women were found to be dengue seropositive. However, transplacental transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.

  7. Performance Evaluation of Commercial Dengue Diagnostic Tests for Early Detection of Dengue in Clinical Samples

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    Tuan Nur Akmalina Mat Jusoh

    2017-01-01

    Full Text Available The shattering rise in dengue virus infections globally has created a need for an accurate and validated rapid diagnostic test for this virus. Rapid diagnostic test (RDT and reverse transcription-polymerase chain reaction (RT-PCR diagnostic detection are useful tools for diagnosis of early dengue infection. We prospectively evaluated the diagnostic performance of nonstructural 1 (NS1 RDT and real-time RT-PCR diagnostic kits in 86 patient serum samples. Thirty-six samples were positive for dengue NS1 antigen while the remaining 50 were negative when tested with enzyme-linked immunosorbent assay (ELISA. Commercially available RDTs for NS1 detection, RTK ProDetect™, and SD Bioline showed high sensitivity of 94% and 89%, respectively, compared with ELISA. GenoAmp® Trioplex Real-Time RT-PCR and RealStar® Dengue RT-PCR tests presented a comparable kappa agreement with 0.722. The result obtained from GenoAmp® Real-Time RT-PCR Dengue test showed that 14 samples harbored dengue virus type 1 (DENV-1, 8 samples harbored DENV-2, 2 samples harbored DENV-3, and 1 sample harbored DENV-4. 1 sample had a double infection with DENV-1 and DENV-2. The NS1 RDTs and real-time RT-PCR tests were found to be a useful diagnostic for early and rapid diagnosis of acute dengue and an excellent surveillance tool in our battle against dengue.

  8. Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses.

    Science.gov (United States)

    Megawati, Dewi; Masyeni, Sri; Yohan, Benediktus; Lestarini, Asri; Hayati, Rahma F; Meutiawati, Febrina; Suryana, Ketut; Widarsa, Tangking; Budiyasa, Dewa G; Budiyasa, Ngurah; Myint, Khin S A; Sasmono, R Tedjo

    2017-05-01

    A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.

  9. Non-HLA gene polymorphisms and their implications on dengue ...

    African Journals Online (AJOL)

    Harapan Harapan

    2012-09-23

    controlled immuno- logical responses. Genetic variants involved in viral entry, replication and innate immunity pathways play an important role in the causal pathway of dengue hemorrhagic fever/dengue shock syndrome.

  10. International Dengue Vaccine Communication and Advocacy: Challenges and Way Forward.

    Science.gov (United States)

    Carvalho, Ana; Van Roy, Rebecca; Andrus, Jon

    2016-01-01

    Dengue vaccine introduction will likely occur soon. However, little has been published on international dengue vaccine communication and advocacy. More effort at the international level is required to review, unify and strategically disseminate dengue vaccine knowledge to endemic countries' decision makers and potential donors. Waiting to plan for the introduction of new vaccines until licensure may delay access in developing countries. Concerted efforts to communicate and advocate for vaccines prior to licensure are likely challenged by unknowns of the use of dengue vaccines and the disease, including uncertainties of vaccine impact, vaccine access and dengue's complex pathogenesis and epidemiology. Nevertheless, the international community has the opportunity to apply previous best practices for vaccine communication and advocacy. The following key strategies will strengthen international dengue vaccine communication and advocacy: consolidating existing coalitions under one strategic umbrella, urgently convening stakeholders to formulate the roadmap for integrated dengue prevention and control, and improving the dissemination of dengue scientific knowledge.

  11. Peripheral gangrene in a case of severe dengue

    African Journals Online (AJOL)

    ergot alkaloids or other related medications. ... The spectrum of disease manifestations in dengue fever is wide. ... dengue shock syndrome and multiorgan failure. .... McGouran RC, Emmerson GA. Symmetrical peripheral gangrene. Br Heart J.

  12. Epidemiological trends of dengue in mainland China, 2005–2015

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    Jimin Sun

    2017-04-01

    Conclusions: Although the number of dengue cases has increased and the affected areas have expanded in recent years, dengue is still an imported disease and does not present an endemic trend in mainland China.

  13. Rare case of acute dengue encephalitis with correlated MRI findings

    International Nuclear Information System (INIS)

    Mathew, Rishi Philip; Basti, Ram Shenoy; Hegde, Pavan; Devdas, Jaidev M.; Khan, Habeeb Ullah; Bukelo, Mario Joseph

    2014-01-01

    Dengue encephalitis is extremely rare, with most patients showing no significant abnormality on neuroimaging (CT/MRI). We report one of the very few documented cases of dengue encephalitis, with abnormal signal intensities on all major sequences on brain MRI.

  14. Stochastic dynamics of dengue epidemics.

    Science.gov (United States)

    de Souza, David R; Tomé, Tânia; Pinho, Suani T R; Barreto, Florisneide R; de Oliveira, Mário J

    2013-01-01

    We use a stochastic Markovian dynamics approach to describe the spreading of vector-transmitted diseases, such as dengue, and the threshold of the disease. The coexistence space is composed of two structures representing the human and mosquito populations. The human population follows a susceptible-infected-recovered (SIR) type dynamics and the mosquito population follows a susceptible-infected-susceptible (SIS) type dynamics. The human infection is caused by infected mosquitoes and vice versa, so that the SIS and SIR dynamics are interconnected. We develop a truncation scheme to solve the evolution equations from which we get the threshold of the disease and the reproductive ratio. The threshold of the disease is also obtained by performing numerical simulations. We found that for certain values of the infection rates the spreading of the disease is impossible, for any death rate of infected mosquitoes.

  15. Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

    Science.gov (United States)

    Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

    2018-04-03

    We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

  16. Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

    Science.gov (United States)

    Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

    2015-01-01

    HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

  17. A case of acute liver failure in dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Rama Biswas

    2013-07-01

    Full Text Available Dengue is an arboviral disease endemic in many parts of the world. The clinical presentation of dengue viral infection ranges from asymptomatic illness to fatal dengue shock syndrome. Although, it is known to cause hepatic involvement, it occasionally results in acute hepatic failure. We report a case of dengue hemorrhagic fever presenting with acute liver failure. The case recovered completely after treatment. Ibrahim Med. Coll. J. 2013; 7(2: 41-42

  18. Dengue in the Americas and Southeast Asia: do they differ?

    Science.gov (United States)

    Halstead, Scott B

    2006-12-01

    The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65,000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

  19. Dengue in the Americas and Southeast Asia: do they differ?

    Directory of Open Access Journals (Sweden)

    Scott B. Halstead

    2006-12-01

    Full Text Available The populations of Southeast Asia (SE Asia and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF, principally in children, whereas in the Americas there were 2.8 million dengue fever (DF cases, principally in adults, and only 65 000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

  20. All Serotypes of Dengue Viruses Circulating in Kuala Lumpur, Malaysia

    OpenAIRE

    M.H. Chew; M.M. Rahman; J. Jelip; M.R. Hassan; I. Isahak

    2012-01-01

    Dengue is a severe disease caused by dengue virus (DENV), transmitted to human being by infected Aedes mosquitoes. It is a major public health concern in Southeast Asia due to its fatality in the form of hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The objective of the study was to isolate and identify dengue virus serotypes prevalent in endemic areas of Kuala Lumpur and Selangor in Malaysia by virus culture, indirect immunoflurecent assay and molecular techniques. A total number ...

  1. Virus isolation for diagnosing dengue virus infections in returning travelers

    NARCIS (Netherlands)

    Teichmann, D.; Göbels, K.; Niedrig, M.; Sim-Brandenburg, J.-W.; Làge-Stehr, J.; Grobusch, M. P.

    2003-01-01

    Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period

  2. Current perspectives on the spread of dengue in India

    Directory of Open Access Journals (Sweden)

    Gupta E

    2014-12-01

    Full Text Available Ekta Gupta, Neha Ballani Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, IndiaAbstract: Dengue fever (DF and dengue hemorrhagic fever (DHF are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with DHF, mainly in Southeast Asia. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. The first major DHF outbreak in the entire nation occurred in 1996 by dengue virus serotype 2, and after a gap of almost a decade, the country faced yet another DF outbreak in the year 2003 by dengue virus serotype 3. A dramatic increase in the number and frequency of outbreaks followed, and, at present, in most of the states of India, dengue is almost endemic. At present, all the four serotypes are seen in circulation, but the predominant serotype keeps changing. Despite this trend, surveillance, reporting, and diagnosis of dengue remain largely passive in India. More active community-based epidemiological studies with intensive vector control and initiatives for dengue vaccine development should be geared up to control the spread of dengue in India. We review here the factors that may have contributed to the changing epidemiology of dengue in India.Keywords: dengue, epidemiology, India, pathogenesis, vaccine

  3. Seroprevalence of Anti-Dengue Virus 2 Serocomplex antibodies in ...

    African Journals Online (AJOL)

    Introduction: There has been a recent increase in the spread of dengue to rural areas. Rural parts of western kenya are naturally prone to mosquito-borne diseases, however, limited research has been documented on infections with dengue. This study therefore investigated the presence of antibodies against dengue virus ...

  4. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

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    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  5. Dengue fatality prediction using data mining | Rahim | Journal of ...

    African Journals Online (AJOL)

    The aim of this research is to study the current implementation of dengue outbreak control in Malaysia and predict dengue fever cases using data mining techniques. Real data on dengue fever and weather are collected from the Ministry of Health in its Perak Tengah district office and Perak Meteorological office respectively ...

  6. Dengue-associated telogen effluvium: A report of 14 patients

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    Chia-Bao Chu

    2017-09-01

    Conclusions: Physicians should be aware of dengue-associated TE especially in dengue endemic areas or after a dengue outbreak. Thorough medical history, examination and laboratory tests should be obtained to yield correct diagnosis or to identify coexistence of two hair diseases.

  7. Fulminant hepatic failure in an infant with severe dengue infection.

    Science.gov (United States)

    Soundravally, R; Narayanan, P; Bhat, B Vishnu; Soundraragavan, Jayanthi; Setia, Sajita

    2010-04-01

    Fulminant hepatic failure due to dengue infection is rare, although mild liver dysfunction is common. Here we report a fatal case of fulminant hepatitis in an infant infected with dengue 3 serotype. Attention must be given to the use of hepatotoxic drugs in some cases of dengue especially in infants.

  8. Spontaneous muscle hematomas in a patient with Dengue hemorrhagic fever

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    Jency Maria Koshy

    2014-01-01

    Full Text Available Dengue hemorrhagic fever (DHF and Dengue shock syndrome manifest in various forms, ranging from petechial skin hemorrhage to life threatening cerebral, pulmonary, gastrointestinal and genitourinary hemorrhages. However it is very rare to have muscle hematomas in DHF. We report a rare case of spontaneous Iliopsoas hematoma complicating Dengue hemorrhagic fever.

  9. Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

    Science.gov (United States)

    Tittarelli, Estefanía; Lusso, Silvina B; Goya, Stephanie; Rojo, Gabriel L; Natale, Mónica I; Viegas, Mariana; Mistchenko, Alicia S; Valinotto, Laura E

    2017-10-01

    The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.

  10. Immature dengue virus : functional properties and potential contribution to disease

    NARCIS (Netherlands)

    Da Silva-Voorham, Júlia Maria

    2013-01-01

    Beter inzicht in mechanismen achter infectieziekte dengue Dengue (‘knokkelkoorts’) is een veelvoorkomende, tropische infectieziekte die wordt overgebracht door muggen. Naar schatting raken jaarlijks zo’n vijftig tot honderd miljoen mensen besmet. Meestal gaat dengue vanzelf over, maar in zo’n

  11. Relato de caso: transmissão vertical de dengue Case report: vertical dengue infection

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    Samara L. C. Maroun

    2008-12-01

    Full Text Available OBJETIVOS: Relatar um caso de transmissão vertical de dengue ocorrido durante epidemia de 2008 pelo vírus tipo II no Rio de Janeiro e revisar a literatura sobre transmissão vertical de dengue. DESCRIÇÃO: Relatamos um caso de transmissão vertical de dengue. Recém-nascido a termo do sexo feminino, peso de nascimento de 3.940 g, foi admitida na unidade de terapia intensiva neonatal com rash cutâneo, hipoatividade e febre no quinto dia de vida. O hemograma evidenciava plaquetopenia importante (38.000 plaquetas. A mãe apresentou quadro clínico compatível com dengue 3 dias antes do parto. Foram colhidos então IgM para dengue da mãe e do recém-nascido, realizados pelo método de ELISA, sendo positivos em ambos. Dengue tipo 2 foi detectado no recém-nascido através de reação em cadeia da polimerase. COMENTÁRIOS: Este relato enfatiza a importância do pediatra estar alerta para a possibilidade de transmissão vertical de dengue iniciando precocemente o tratamento.OBJECTIVES: To report a case of vertical dengue infection in a newborn from Rio de Janeiro, Brazil, and to review the literature concerning this problem. DESCRIPTION: We report a case of vertical dengue infection. Female neonate, birth weight 3,940 g, term, was admitted to a neonatal intensive care unit on the fifth day of life with fever and erythematous rash. Her mother had had dengue fever 3 days before delivery. Her platelet count was 38,000, dropping to 15,000. She did not have any hemorrhagic episodes, including cerebral hemorrhages. Anti-dengue antibodies (IgM were positive in the mother and infant. Dengue type 2 was detected in the infant using polymerase chain reaction. COMMENTS: This report emphasizes that pediatricians should be aware of the possibility of vertical dengue infection so that early management can be instituted.

  12. Validation of dengue infection severity score

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    Pongpan S

    2014-03-01

    Full Text Available Surangrat Pongpan,1,2 Jayanton Patumanond,3 Apichart Wisitwong,4 Chamaiporn Tawichasri,5 Sirianong Namwongprom1,6 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Occupational Medicine, Phrae Hospital, Phrae, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Social Medicine, Sawanpracharak Hospital, Nakorn Sawan, Thailand; 5Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand; 6Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: To validate a simple scoring system to classify dengue viral infection severity to patients in different settings. Methods: The developed scoring system derived from 777 patients from three tertiary-care hospitals was applied to 400 patients in the validation data obtained from another three tertiary-care hospitals. Percentage of correct classification, underestimation, and overestimation was compared. The score discriminative performance in the two datasets was compared by analysis of areas under the receiver operating characteristic curves. Results: Patients in the validation data were different from those in the development data in some aspects. In the validation data, classifying patients into three severity levels (dengue fever, dengue hemorrhagic fever, and dengue shock syndrome yielded 50.8% correct prediction (versus 60.7% in the development data, with clinically acceptable underestimation (18.6% versus 25.7% and overestimation (30.8% versus 13.5%. Despite the difference in predictive performances between the validation and the development data, the overall prediction of the scoring system is considered high. Conclusion: The developed severity score may be applied to classify patients with dengue viral infection into three severity levels with clinically acceptable under- or overestimation. Its impact when used in routine

  13. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study

    OpenAIRE

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. Methods A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period o...

  14. Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

    Science.gov (United States)

    Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

    2010-11-01

    To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

  15. Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

    International Nuclear Information System (INIS)

    Kidwai, A.A.; Jamal, Q.; Mehrunnisa, S.; Farooqi, F.R.

    2010-01-01

    Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

  16. Dengue Virus Genome Uncoating Requires Ubiquitination.

    Science.gov (United States)

    Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

    2016-06-28

    The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

  17. Dengue vaccines: Are they safe for travelers?

    Science.gov (United States)

    Halstead, Scott B; Aguiar, Maira

    2016-01-01

    The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Activity of andrographolide against dengue virus.

    Science.gov (United States)

    Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

    2017-03-01

    Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. First Iranian imported case of dengue

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    Masoud Mardani

    2013-01-01

    Full Text Available Dengue fever, a mosquito-borne flavivirus infection, is endemic in Southeast Asia. Currently, incidences have been increasing among adults. There have been no published reports of dengue fever from Iran. Widespread connection between different countries may predispose them for acquisition of infection. The patient was a 58-year-old Iranian woman with acute unexplained high-grade fever for 4 days, associated with skin rash, after returning from Southeast Asia. CBC showed WBC = 1600/mm 3 and platelet count 99,000/mm 3 . The patient also had hematuria. ELISA immunoglobulin M (IgM antibodies to dengue and serum RT-PCR for dengue virus was positive. The patient managed with conservative treatment and due to good general condition and improvement specific antiviral treatment was not started. She became afebrile at the 3 rd day of hospitalization and discharged with good general condition on fourth day. She was afebrile after two weeks follow-up. Dengue fever has been increasing among adults. It should be suspected, when a patient presents with acute febrile illness and skin rashes returning from endemic region. Conservative treatment may be conducted in uncomplicated cases .

  20. Dengue: muscle biopsy findings in 15 patients

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    S.M.F. Malheiros

    1993-06-01

    Full Text Available Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry in 15 patients (4 males, median age 23 years (range 14-47 with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

  1. Spatial patterns of dengue cases in Brazil.

    Directory of Open Access Journals (Sweden)

    Fernando Jose Antonio

    Full Text Available Dengue infection plays a central role in our society, since it is the most prevalent vector-borne viral disease affecting humans. We statistically investigated patterns concerning the spatial spreading of dengue epidemics in Brazil, as well as their temporal evolution in all Brazilian municipalities for a period of 12 years. We showed that the distributions of cases in municipalities follow power laws persistent in time and that the infection scales linearly with the population of the municipalities. We also found that the average number of dengue cases does not have a clear dependence on the longitudinal position of municipalities. On the other hand, we found that the average distribution of cases varies with the latitudinal position of municipalities, displaying an almost constant growth from high latitudes until reaching the Tropic of Capricorn leveling to a plateau closer to the Equator. We also characterized the spatial correlation of the number of dengue cases between pairs of municipalities, where our results showed that the spatial correlation function decays with the increase of distance between municipalities, following a power-law with an exponential cut-off. This regime leads to a typical dengue traveling distance. Finally, we considered modeling this last behaviour within the framework of a Edwards-Wilkinson equation with a fractional derivative on space.

  2. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans.

    Directory of Open Access Journals (Sweden)

    Beatriz Sierra

    2017-02-01

    Full Text Available Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease.

  3. Dengue virus serotype 2 infection alters midgut and carcass gene expression in the Asian tiger mosquito, Aedes albopictus.

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    Hitoshi Tsujimoto

    Full Text Available The Asian tiger mosquito, Aedes albopictus is currently an important vector for dengue, chikungunya and Zika virus, and its role in transmission of arthropod-borne viruses (arboviruses may increase in the future due to its ability to colonize temperate regions. In contrast to Aedes aegypti, the dominant vector of dengue, chikungunya and Zika virus, genetic responses of Ae. albopictus upon infection with an arbovirus are not well characterized. Here we present a study of the changes in transcript expression in Ae. albopictus exposed to dengue virus serotype 2 via feeding on an artificial bloodmeal.We isolated midguts and midgut-free carcasses of Ae. albopictus fed on bloodmeals containing dengue virus as well as controls fed on virus-free control meals at day 1 and day 5 post-feeding. We confirmed infection of midguts from mosquitoes sampled on day 5 post-feeding via RT-PCR. RNAseq analysis revealed dynamic modulation of the expression of several putative immunity and dengue virus-responsive genes, some of whose expression was verified by qRT-PCR. For example, a serine protease gene was up-regulated in the midgut at 1 day post infection, which may potentially enhance mosquito susceptibility to dengue infection, while 14 leucine-rich repeat genes, previously shown to be involved in mosquito antiviral defenses, were down-regulated in the carcass at 5 days post infection. The number of significantly modulated genes decreased over time in midguts and increased in carcasses.Dengue virus exposure results in the modulation of genes in a time- and site-specific manner. Previous literature on the interaction between mosquitoes and mosquito-borne pathogens suggests that most of the changes that occurred in Ae. albopictus exposed to DENV would favor virus infection. Many genes identified in this study warrant further characterization to understand their role in viral manipulation of and antiviral response of Ae. albopictus.

  4. Epidemiological update on the dengue situation in the Western Pacific Region, 2012.

    Science.gov (United States)

    Arima, Yuzo; Chiew, May; Matsui, Tamano

    2015-01-01

    Dengue has caused a substantial public health burden in the Western Pacific Region. To assess this burden and regional trends, data were collated and summarized from indicator-based surveillance systems on dengue cases and deaths from countries and areas in the Western Pacific Region. In 2012, dengue notifications continued to increase with 356,838 dengue cases reported in the Region (relative to 244,855 cases reported in 2011) of which 1248 died. In the Asia subregion, the notification rate was highest in Cambodia, the Philippines and the Lao People's Democratic Republic (316.2, 198.9 and 162.4 per 100,000 population, respectively), and in the Pacific island countries and areas, the notification rate was highest in Niue, the Marshall Islands and the Federated States of Micronesia (8556.0, 337.0 and 265.1 per 100,000 population, respectively). All four serotypes were circulating in the Region in 2012 with considerable variabilitiy in distribution. Regional surveillance provides important information to enhance situational awareness, conduct risk assessments and improve preparedness activities.

  5. Epidemiological update on the dengue situation in the Western Pacific Region, 2012

    Directory of Open Access Journals (Sweden)

    Yuzo Arima

    2015-04-01

    Full Text Available Dengue has caused a substantial public health burden in the Western Pacific Region. To assess this burden and regional trends, data were collated and summarized from indicator-based surveillance systems on dengue cases and deaths from countries and areas in the Western Pacific Region. In 2012, dengue notifications continued to increase with 356 838 dengue cases reported in the Region (relative to 244 855 cases reported in 2011 of which 1248 died. In the Asia subregion, the notification rate was highest in Cambodia, the Philippines and the Lao People’s Democratic Republic (316.2, 198.9 and 162.4 per 100 000 population, respectively, and in the Pacific island countries and areas, the notification rate was highest in Niue, the Marshall Islands and the Federated States of Micronesia (8556.0, 337.0 and 265.1 per 100 000 population, respectively. All four serotypes were circulating in the Region in 2012 with considerable variabilitiy in distribution. Regional surveillance provides important information to enhance situational awareness, conduct risk assessments and improve preparedness activities.

  6. Current Status of Dengue Therapeutics Research and Development.

    Science.gov (United States)

    Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

    2017-03-01

    Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. Dengue fever with rectus sheath hematoma: A case report

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    Anurag Sharma

    2014-01-01

    Full Text Available Dengue fever, also known as breakbone fever, is an infectious tropical disease caused by the Dengue virus. It is associated with a number of complications, which are well documented. However, Dengue fever associated with rectus sheath hematoma (RSH is a very rare complication. Only one case report has been published prior supporting the association of Dengue fever with RSH. We report a case of Dengue fever who presented with RSH and was successfully treated conservatively. RSH is also an uncommon cause of acute abdominal pain. It is accumulation of blood in the sheath of the rectus abdominis, secondary to rupture of an epigastric vessel or muscle tear.

  8. Dengue viruses in Brazil, 1986-2006 Virus del dengue en Brasil, 1986-2006

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    Rita Maria Ribeiro Nogueira

    2007-11-01

    Full Text Available A total of 4 243 049 dengue cases have been reported in Brazil between 1981 and 2006, including 5 817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.En Brasil se han notificado 4 243 049 casos de dengue entre 1981 y 2006, de ellos 5 817 casos de dengue hemorrágico/síndrome de choque por dengue (DH/SCD y un total de 338 casos mortales. A pesar de que la enfermedad ha afectado a todas las regiones brasileñas, el mayor número de casos se ha notificado en las regiones nororiental y suroriental. Los virus del dengue (DENV 1 y 4 se aislaron por primera vez en la región amazónica de Brasil en 1981 y 1982. La enfermedad se convirtió en un problema nacional de salud pública después de los brotes de DENV-1 y DENV-2 en el Estado de Río de Janeiro en 1986 y 1990, respectivamente. La introducción del DENV-3 en 2000, también en el Estado de Río de Janeiro, llevó a una grave epidemia con 288 245 casos notificados de dengue y 91 muertes. Las cepas del virus identificadas durante la epidemia de 2002 demostraron que el DENV-3 ha

  9. Metformin Use and Severe Dengue in Diabetic Adults.

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    Htun, Htet Lin; Yeo, Tsin Wen; Tam, Clarence C; Pang, Junxiong; Leo, Yee Sin; Lye, David C

    2018-02-20

    Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37-0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49-0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.

  10. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

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    Parkash, Om; Hanim Shueb, Rafidah

    2015-01-01

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

  11. [Imported dengue: an emerging arbovirosis in Spain].

    Science.gov (United States)

    Ramos Geldres, T T; García López-Hortelano, M; Baquero-Artigao, F; Montero Vega, D; López Quintana, B; Mellado Peña, M J

    2015-01-01

    Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  12. Dengue fever in pregnancy: a case report

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    Phupong Vorapong

    2001-12-01

    Full Text Available Abstract Background Dengue, a mosquito-borne flavivirus infection, is endemic in Southeast Asia. Currently, the incidence has been increasing among adults. Case presentation A 26-year-old Thai woman, G1P0 31 weeks pregnancy, presented with epigastric pain for 1 day. She also had a high-grade fever for 4 days. The physical examination, complete blood counts as well as serology confirmed dengue fever. The patient was under conservative treatment despite severe thrombocytopenia. She was well at the 3rd day of discharge and 1-week follow-up. The pregnancy continued until term without any complication and she delivered vaginally a healthy female baby. Conclusions More cases of dengue infection in pregnancy can be found due to the increasing incidence during adulthood. It should be suspected when a pregnant woman presents with symptoms and signs like in a non-pregnant. Conservative treatment should be conducted unless there are any complications.

  13. Anti dengue education: a experience report

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    Marise Maleck

    2017-11-01

    Full Text Available Aedes aegypti (L., 1762 is the main vector recognized as a dengue virus transmitter. This vector, once adapted to human habits, finds it easy to reproduce in homes that have open water containers, easily found in city streets and garbage dumps. Educational institutions play a fundamental role in the formation of young people as disseminator citizens in favor of health improvement practices. In order to promote education for the control of the dengue virus mosquito vector, this work was developed through recreational and educational activities in Central-South Rio de Janeiro state public and private schools, cities, cultural centers and public spaces. The results showed positive responses above 80% of the Aedes-dengue-control issue. The project had 2500 participants. The Antidengue Education Project demonstrated that education is an effective tool regarding education, health and the environment.

  14. Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient

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    Isern Sharon

    2010-02-01

    Full Text Available Abstract Background Antibodies produced in response to infection with any of the four serotypes of dengue virus generally provide homotypic immunity. However, prior infection or circulating maternal antibodies can also mediate a non-protective antibody response that can enhance the course of disease in a subsequent heterotypic infection. Naturally occurring human monoclonal antibodies can help us understand the protective and pathogenic roles of the humoral immune system in dengue virus infection. Results Epstein-Barr Virus (EBV transformation of B cells isolated from the peripheral blood of a human subject with previous dengue infection was performed. B cell cultures were screened by ELISA for antibodies to dengue (DENV envelope (E protein. ELISA positive cultures were cloned by limiting dilution. Three IgG1 human monoclonal antibodies (HMAbs were purified and their binding specificity to E protein was verified by ELISA and biolayer interferometry. Neutralization and enhancement assays were conducted in epithelial and macrophage-like cell lines, respectively. All three HMAbs bound to E from at least two of the four DENV serotypes, one of the HMAbs was neutralizing, and all were able to enhance DENV infection. Conclusions HMAbs against DENV can be successfully generated by EBV transformation of B cells from patients at least two years after naturally acquired DENV infections. These antibodies show different patterns of cross-reactivity, neutralizing, and enhancement activity.

  15. [Epidemiological dynamics of Dengue on Easter Island].

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    Canals, Mauricio; González, Christian; Canals, Andrea; Figueroa, Daniela

    2012-08-01

    Dengue is considered an emerging disease with an increasing prevalence especially in South America. In 2002, an epidemic of classic Dengue (DENV-1) occurred unexpectedly on Easter Island, where it had never been detected before. It reappeared in 2006-2007 and 2008, 2009 and 2011. The aim of this study was to estimate the most relevant parameters of the epidemiological dynamics of transmission of Dengue on Easter Island and to model the dynamics since 2002, comparing the predictions with the actual situation observed. Of the total cases, 52.27% were females and 47.73% men. The average age of infection was 31.38 ± 18.37 years, similar in men and women. We estimated the reproductive number R0 = 3.005 with an IC0,95 = [1.92, 4.61]. The inter-epidemic period reached an estimated T = 5.20 to 6.8 years. The case simulation showed recurrent epidemics with decreasing magnitude (damped oscillations), which is a known phenomenon in models of dengue and malaria. There was good qualitative fit to the epidemiological dynamics from 2002 onwards. It accurately predicted the rise in cases between 2006 and 2011. The predicted number of cases during the 2002 epidemic is greater than the confirmed cases and the predicted epidemic was faster than notified cases. Interepidemic period in the simulation was 6.72 years between 2002 and 2008 and 4.68 years between 2008 and 2013. From the theoretical perspective, the first epidemic had affected 94% of the population (approximately 3500 cases), but 639 were reported suggesting underreporting and a lot of sub-clinical cases occurred. Future epidemic of decreasing size are expected, although the main danger are epidemics of hemorrhagic dengue fever resulting from the introduction of different dengue virus serotypes.

  16. Factors determining dengue outbreak in Malaysia.

    Science.gov (United States)

    Ahmad, Rohani; Suzilah, Ismail; Wan Najdah, Wan Mohamad Ali; Topek, Omar; Mustafakamal, Ibrahim; Lee, Han Lim

    2018-01-01

    A large scale study was conducted to elucidate the true relationship among entomological, epidemiological and environmental factors that contributed to dengue outbreak in Malaysia. Two large areas (Selayang and Bandar Baru Bangi) were selected in this study based on five consecutive years of high dengue cases. Entomological data were collected using ovitraps where the number of larvae was used to reflect Aedes mosquito population size; followed by RT-PCR screening to detect and serotype dengue virus in mosquitoes. Notified cases, date of disease onset, and number and type of the interventions were used as epidemiological endpoint, while rainfall, temperature, relative humidity and air pollution index (API) were indicators for environmental data. The field study was conducted during 81 weeks of data collection. Correlation and Autoregressive Distributed Lag Model were used to determine the relationship. The study showed that, notified cases were indirectly related with the environmental data, but shifted one week, i.e. last 3 weeks positive PCR; last 4 weeks rainfall; last 3 weeks maximum relative humidity; last 3 weeks minimum and maximum temperature; and last 4 weeks air pollution index (API), respectively. Notified cases were also related with next week intervention, while conventional intervention only happened 4 weeks after larvae were found, indicating ample time for dengue transmission. Based on a significant relationship among the three factors (epidemiological, entomological and environmental), estimated Autoregressive Distributed Lag (ADL) model for both locations produced high accuracy 84.9% for Selayang and 84.1% for Bandar Baru Bangi in predicting the actual notified cases. Hence, such model can be used in forestalling dengue outbreak and acts as an early warning system. The existence of relationships among the entomological, epidemiological and environmental factors can be used to build an early warning system for the prediction of dengue outbreak so

  17. Dengue vaccines: Challenges, development, current status and prospects

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    A Ghosh

    2015-01-01

    Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.

  18. Dengue infection and miscarriage: a prospective case control study.

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    Peng Chiong Tan

    Full Text Available BACKGROUND: Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known. METHOD: We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1 antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy plus 45 controls (39 lost to follow up and six subsequent late miscarriages were excluded from analysis. FINDINGS: Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection was positive in 6/115 (5·2% cases and 5/296 (1·7% controls RR 3·1 (95% CI 1·0-10 P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2-14 P = 0·023. INTERPRETATION: Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.

  19. FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

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    Soegeng Soegijanto

    2018-04-01

    Full Text Available Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to

  20. Cost of dengue outbreaks: literature review and country case studies.

    Science.gov (United States)

    Stahl, Hans-Christian; Butenschoen, Vicki Marie; Tran, Hien Tinh; Gozzer, Ernesto; Skewes, Ronald; Mahendradhata, Yodi; Runge-Ranzinger, Silvia; Kroeger, Axel; Farlow, Andrew

    2013-11-06

    Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save--through early response activities--resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems.The country case studies--conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the different cost components (vector control

  1. Cost of dengue outbreaks: literature review and country case studies

    Science.gov (United States)

    2013-01-01

    Background Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save – through early response activities – resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Methods Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Results Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems. The country case studies – conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the

  2. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil.

    Science.gov (United States)

    Ferraz, Fernanda Oliveira; Bomfim, Maria Rosa Quaresma; Totola, Antônio Helvécio; Ávila, Thiago Vinícius; Cisalpino, Daniel; Pessanha, José Eduardo Marques; da Glória de Souza, Danielle; Teixeira Júnior, Antônio Lúcio; Nogueira, Maurício Lacerda; Bruna-Romero, Oscar; Teixeira, Mauro Martins

    2013-09-01

    Dengue is a widely spread arboviral disease in tropical and subtropical regions of the world. Dengue fever presents clinical characteristics similar to other febrile illness. Thus laboratory diagnosis is important for adequate management of the disease. The present study was designed to evaluate the diagnostic performance of real-time PCR and serological methods for dengue in a real epidemic context. Clinical data and blood samples were collected from consecutive patients with suspected dengue who attended a primary health care unit in Belo Horizonte, Brazil. Serologic methods and real-time PCR were performed in serum samples to confirm dengue diagnosis. Among the 181 consecutive patients enrolled in this study with suspected dengue, 146 were considered positive by serological criteria (positive NS1 ELISA and/or anti-dengue IgM ELISA) and 138 were positive by real-time PCR. Clinical criteria were not sufficient for distinguishing between dengue and non-dengue febrile illness. The PCR reaction was pre-optimized using samples from patients with known viral infection. It had similar sensitivity compared to NS1 ELISA (88% and 89%, respectively). We also evaluated three commercial lateral flow immunochromatographic tests for NS1 detection (BIOEASY, BIORAD and PANBIO). All three tests showed high sensitivity (94%, 91% and 81%, respectively) for dengue diagnosis. According to our results it can be suggested that lateral flow tests for NS1 detection are the most feasible methods for early diagnosis of dengue. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Dengue en Panamá, 1993

    OpenAIRE

    QUIROZ, EVELIA; ORTEGA, MARITZA; GUZMÁN, MARÍA GUADALUPE; VÁZQUEZ, SUSANA; PELEGRINO, JOSÉ LUIS; CAMPOS, CORNELIO; BAYARD, VICENTE; VÁZQUEZ, MANUEL; KOURÍ, GUSTAVO

    1997-01-01

    Hasta 1993, Panamá era el único país de Centroamérica que había detectado transmisión autóctona de virus dengue sin experimentar una epidemia explosiva, pese a estar reinfestado con el mosquito Aedes aegypti desde 1985. En este trabajo se describen las características de este primer brote reportado el 19 de noviembre de 1993 y se demuestra que las epidemias se presentan a pesar de mantener un Programa de Vigilancia y Control para Dengue -que contempla bajos niveles de infestación del Aedes ae...

  4. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

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    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  5. Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges.

    Science.gov (United States)

    Guzman, María G; Kouri, Gustavo

    2003-05-01

    The incidence of dengue and dengue hemorrhagic fever (DF/DHF) has increased significantly over the last decades. Yearly, an estimated 50-100 million cases of DF and about 250000-500000 cases of DHF occur worldwide. The epidemiological situation in Latin America now resembles that in Southeast Asia. Here, the main clinical, epidemiological and virological observations in the American region are presented and compared with those previously reported from Southeast Asia. During 2002, more than 30 Latin American countries reported over 1000000 DF cases. DHF occurred in 20 countries with more than 17000 DHF cases, including 225 fatalities. The co-circulation of multiple serotypes has been reported from many countries. In the Americas, DHF is observed both in children and adults; secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for this severe form of the disease. However, some new risk factors such as the interval of dengue virus infections and the ethnicity and underlying chronic conditions of the patient have also been identified. The sequence of dengue virus infections and association with certain genotypes are further factors of importance. We also discuss the control and prevention strategies. In conclusion, without urgent action for the prevention and control of dengue/DHF and its vector, the current situation will worsen and, more dramatical, there is a risk of the urbanization of yellow fever.

  6. System Dynamics based Dengue modeling environment to simulate evolution of Dengue infection under different climate scenarios

    Science.gov (United States)

    Anwar, R.; Khan, R.; Usmani, M.; Colwell, R. R.; Jutla, A.

    2017-12-01

    Vector borne infectious diseases such as Dengue, Zika and Chikungunya remain a public health threat. An estimate of the World Health Organization (WHO) suggests that about 2.5 billion people, representing ca. 40% of human population,are at increased risk of dengue; with more than 100 million infection cases every year. Vector-borne infections cannot be eradicated since disease causing pathogens survive in the environment. Over the last few decades dengue infection has been reported in more than 100 countries and is expanding geographically. Female Ae. Aegypti mosquito, the daytime active and a major vector for dengue virus, is associated with urban population density and regional climatic processes. However, mathematical quantification of relationships on abundance of vectors and climatic processes remain a challenge, particularly in regions where such data are not routinely collected. Here, using system dynamics based feedback mechanism, an algorithm integrating knowledge from entomological, meteorological and epidemiological processes is developed that has potential to provide ensemble simulations on risk of occurrence of dengue infection in human population. Using dataset from satellite remote sensing, the algorithm was calibrated and validated using actual dengue case data of Iquitos, Peru. We will show results on model capabilities in capturing initiation and peak in the observed time series. In addition, results from several simulation scenarios under different climatic conditions will be discussed.

  7. Penentuan Serotipe Virus Dengue dan Gambaran Manifestasi Klinis serta Hematologi Rutin pada Infeksi Virus Dengue

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    Basti Andriyoko

    2012-12-01

    Full Text Available All DENV serotypes can cause a spectrum of disease from dengue fever (DF to dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. It is difficult to differentiate clinical characteristicand hematologic result for each serotype. Aim of this study were to determine dengue serotype and describe clinical manifestation of DF, DHF, DSS and routine hematologic results, i.e.haemoglobin, hematocrit, leukocyte, and thrombocyte in each serotype. This study was conducted at Dr. Hasan Sadikin Hospital Bandung from March 2010 until July 2011. Subjects were dengue patients aged >14 years with a history of fever <5 days. Blood samples were taken for serotype determination by reverse transcription polymerase chain reaction (RT-PCR followed by semi-nested PCR. Clinical manifestation data and haematologic result were obtained from medical records. This was a descriptive study. Seventy five patients were included in this study. Dengue serotype can be detected in 27 (36% samples with DENV-3 (13 were dominating followed by DENV-2 (8, DENV-4 (4, and DENV-1 (2. DHF was mainly found in DENV-3. DENV-2 gavethe highest decrease in hemoglobin, highest percentage increase in haematocrit, lowest leukocyte, and lowest thrombocyte. In conclusion, all 4 serotypes are found in RSUP Dr. Hasan Sadikin Hospital Bandung with DENV-3 domination. DHF is mainly caused by DENV-3.

  8. The prevention and control of dengue after Typhoon Haiyan

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    Charito Aumentado

    2015-11-01

    Full Text Available Objective: Many of the areas in the Philippines affected by Typhoon Haiyan are endemic for dengue; therefore, dengue prevention was a priority in the initial post-disaster risk assessment. We describe the dengue prevention and response strategies applied after Haiyan. Methods: The dengue response was implemented by a wide range of national and international stakeholders. Priorities included the rapid re-establishment of an effective surveillance system to quickly identify new dengue cases, monitor trends and determine the geographical distribution of cases. Dengue rapid diagnostic tests (RDTs were distributed to sentinel health facilities, and comprehensive vector control activities and entomological surveys were implemented. Several training sessions for key stakeholders and awareness campaigns for communities were organized. Results: There were RDT-positive dengue cases reported from urban and semi-urban areas where entomological surveys also confirmed a high density of Aedes aegypti mosquitoes. Although there was an increase in dengue cases in January 2014, the number of cases remained below the epidemic threshold throughout the remaining months of 2014. Discussion: There was no large outbreak of dengue after Typhoon Haiyan, possibly due to the targeted, multifaceted and rapid response for dengue after Haiyan. However, surveillance differed after Haiyan, making comparisons with previous years difficult. Multiple players contributed to the response that was also facilitated by close communication and coordination within the Health Cluster.

  9. Cost of Dengue Vector Control Activities in Malaysia

    Science.gov (United States)

    Packierisamy, P. Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K.; Halasa, Yara A.; Shepard, Donald S.

    2015-01-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. PMID:26416116

  10. Cost of Dengue Vector Control Activities in Malaysia.

    Science.gov (United States)

    Packierisamy, P Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K; Halasa, Yara A; Shepard, Donald S

    2015-11-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. © The American Society of Tropical Medicine and Hygiene.

  11. Risk factors for concurrent bacteremia in adult patients with dengue.

    Science.gov (United States)

    Thein, Tun-Linn; Ng, Ee-Ling; Yeang, Ming S; Leo, Yee-Sin; Lye, David C

    2017-06-01

    Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. We conducted a retrospective case-control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill. Copyright © 2015. Published by Elsevier B.V.

  12. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

    OpenAIRE

    Idrees, Sobia; Ashfaq, Usman A

    2012-01-01

    Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to e...

  13. Dengue Fever in the United States

    Centers for Disease Control (CDC) Podcasts

    2012-04-09

    Dr. Amesh Adalja, an associate at the Center for Biosecurity and clinical assistant professor at the University of Pittsburgh School, of Medicine, discusses dengue fever outbreaks in the United States.  Created: 4/9/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/16/2012.

  14. Multiobjective Genetic Algorithm applied to dengue control.

    Science.gov (United States)

    Florentino, Helenice O; Cantane, Daniela R; Santos, Fernando L P; Bannwart, Bettina F

    2014-12-01

    Dengue fever is an infectious disease caused by a virus of the Flaviridae family and transmitted to the person by a mosquito of the genus Aedes aegypti. This disease has been a global public health problem because a single mosquito can infect up to 300 people and between 50 and 100 million people are infected annually on all continents. Thus, dengue fever is currently a subject of research, whether in the search for vaccines and treatments for the disease or efficient and economical forms of mosquito control. The current study aims to study techniques of multiobjective optimization to assist in solving problems involving the control of the mosquito that transmits dengue fever. The population dynamics of the mosquito is studied in order to understand the epidemic phenomenon and suggest strategies of multiobjective programming for mosquito control. A Multiobjective Genetic Algorithm (MGA_DENGUE) is proposed to solve the optimization model treated here and we discuss the computational results obtained from the application of this technique. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Dengue vaccine: come let's fight the menace.

    Science.gov (United States)

    Chawla, Sumit; Sahoo, Soumya Swaroop; Singh, Inderjeet; Verma, Madhur; Gupta, Vikas; Kumari, Sneh

    2015-01-01

    Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.

  16. Dengue fever | Tavodova | South Sudan Medical Journal

    African Journals Online (AJOL)

    South Sudan Medical Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 5, No 1 (2012) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Dengue fever. Milada Tavodova. Abstract. No Abstract ...

  17. Immature dengue virus: a veiled pathogen?

    Directory of Open Access Journals (Sweden)

    Izabela A Rodenhuis-Zybert

    2010-01-01

    Full Text Available Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.

  18. Dengue Virus Genome Uncoating Requires Ubiquitination

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    Laura A. Byk

    2016-06-01

    Full Text Available The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process.

  19. Dengue in the elderly: a review.

    Science.gov (United States)

    Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

    2017-08-01

    Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

  20. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    Directory of Open Access Journals (Sweden)

    Michael J Conway

    2016-09-01

    Full Text Available Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.

  1. Manifestações mucocutâneas da dengue Mucocutaneous manifestations of dengue

    Directory of Open Access Journals (Sweden)

    Omar Lupi

    2007-08-01

    Full Text Available Dengue é doença viral sistêmica que ocorre de forma epidêmica em áreas tropicais e subtropicais da Ásia, Américas e África. O vírus da dengue pertence ao gênero Flavivirus e à família Flaviviridae (arbovírus do grupo B. Aedes aegypti é o principal vetor e verdadeiro reservatório. A febre na dengue clássica persiste por período de dois a cinco dias com cefaléia intensa, mialgia, artralgia e dor retro-orbital. Alterações cutâneas incluem diversos achados como erupção morbiliforme que pode ser pruriginosa e que gera descamação residual, algumas manifestações hemorrágicas discretas como epistaxe, petéquias e sangramento gengival. Extravasamento capilar de plasma é responsável pela hemoconcentração e trombocitopenia observadas e que caracterizam a dengue hemorrágica. Manifestações cutâneas da dengue hemorrágica incluem lesões hemorrágicas disseminadas como petéquias e equimoses, mas também instabilidade hemodinâmica com pulso filiforme, pressão arterial convergente, extremidades frias, confusão mental e choque.Dengue fever is a systemic viral disease that occurs epidemically in tropical and subtropical regions of Asia, Americas and Africa. The dengue virus belongs to the genus Flavivirus of the family Flaviviridae (group B arbovirus. Aedes aegypti is the major vector and the true reservoir for the virus. Classic dengue fever lasts for two-five days, with severe headache, intense myalgia, arthralgia and retro-orbital pain. Cutaneous alterations include several findings such as a diffuse morbilliform rash that may be pruritic and heals with desquamation, and minor bleeding phenomena such as epistaxis, petechiae, and gingival bleeding. Diffuse capillary leakage of plasma is responsible for the hemoconcentration and thrombocytopenia that characterize dengue hemorrhagic fever. Cutaneous manifestations of dengue hemorrhagic fever include many disseminated hemorrhagic lesions such as petechiae and ecchymoses, but

  2. A epidemia de dengue/dengue hemorrágico no município do Rio de Janeiro, 2001/2002 The epidemic of dengue and hemorrhagic dengue fever in the city of Rio de Janeiro, 2001/2002

    Directory of Open Access Journals (Sweden)

    Clarisse Guimarães Casali

    2004-08-01

    Full Text Available O objetivo deste estudo foi avaliar a ocorrência dos principais sinais e sintomas dos casos de dengue clássico e dengue hemorrágico na epidemia de 2001-2002 do município do Rio de Janeiro. Foram analisados os 155.242 casos notificados ao Sistema de Informações de Agravos de Notificação, desde janeiro/2001, até junho/2002; deste total, excluindo-se os ignorados, 81.327 casos foram classificados como dengue clássico e 958 como dengue hemorrágico, com um total de 54 óbitos. Avaliaram-se as variáveis referentes à sintomatologia da doença. Manifestações gerais como febre, cefaléia, prostração, mialgia, náuseas e dor retro-orbitária tiveram alta incidência tanto no dengue clássico como no dengue hemorrágico. Por outro lado, manifestações hemorrágicas e algumas de maior gravidade como choque, hemorragia digestiva, petéquias, epistaxe, dor abdominal e derrame pleural, estiveram significativamente associadas ao dengue hemorrágico. Além disso, a evolução do quadro clínico para o óbito foi 34,8 vezes maior no dengue hemorrágico que no dengue clássico (OR=34,8; IC 19,7-61,3.The following study was intended to evaluate the occurrence of typical signs and symptoms in the cases of classic dengue and hemorrhagic dengue fever, during the 2001-2002 epidemic in the city of Rio de Janeiro. The authors reviewed 155,242 cases notified to the Information System of Notification Diseases, from January/2001 to June/2002: 81,327 cases were classified as classic dengue and 958 as hemorrhagic dengue fever, with a total of 60 deaths. Common symptoms, such as fever, headache, prostration, myalgia, nausea and retro-orbital pain, had a high incidence in both classic and hemorrhagic dengue fever. On the other hand, hemorrhagic signs and other signs of severe disease, such as shock, gastrointestinal bleeding, petechiae, epistaxis, abdominal pain and pleural effusion, were strongly associated to hemorrhagic dengue fever. Besides, the occurrence

  3. Acute neuromuscular weakness associated with dengue infection

    Directory of Open Access Journals (Sweden)

    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  4. Underrecognition of Dengue during 2013 Epidemic in Luanda, Angola.

    Science.gov (United States)

    Sharp, Tyler M; Moreira, Rosa; Soares, Maria José; Miguel da Costa, Lúis; Mann, Jennifer; DeLorey, Mark; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Colón, Candimar; Margolis, Harold S; de Caravalho, Adelaide; Tomashek, Kay M

    2015-08-01

    During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic test-positive cases were reported to the Ministry of Health. To better understand the magnitude of the epidemic and identify risk factors for dengue virus (DENV) infection, we conducted cluster surveys around households of case-patients and randomly selected households 6 weeks after the peak of the epidemic. Of 173 case cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247 random cluster participants, 25 (10%) had evidence of recent DENV infection. Of 13 recently infected participants who had a recent febrile illness, 7 (54%) had sought medical care, and 1 (14%) was hospitalized with symptoms consistent with severe dengue; however, none received a diagnosis of dengue. Behavior associated with protection from DENV infection included recent use of mosquito repellent or a bed net. These findings suggest that the 2013 dengue epidemic was larger than indicated by passive surveillance data.

  5. Dengue Haemorrhagic Encephalitis: Rare Case Report with Review of Literature.

    Science.gov (United States)

    Kutiyal, Aditya Singh; Malik, Chetanya; Hyanki, Gitika

    2017-07-01

    Dengue is an endemic arboviral infection prevalent especially in tropical countries including Southern and Southeast Asia. Central Nervous System (CNS) involvement in dengue infection is uncommon. Haemorrhagic encephalitis is a rare presentation in dengue. This is a case of a 58-year-old male who presented with fever, petechial rash and altered sensorium. Dengue serology IgM was reactive and MRI brain was suggestive of haemorrhagic encephalitis. Patient was managed in Intensive Care Unit (ICU) but eventually succumbed to his illness. We report this fatal outcome of a common viral infection with unusual neurological presentation to propose an association between dengue and neurotropism and the need to look at dengue infection beyond its classical features.

  6. A Case of Dengue Maculopathy with Spontaneous Recovery

    Directory of Open Access Journals (Sweden)

    Fiona Oi-jing Luk

    2013-06-01

    Full Text Available Purpose: To report a case of dengue maculopathy, which resolved spontaneously without treatment. Methods: A 25-year-old female patient with good past health was admitted to a general hospital in Hong Kong with fever of unknown origin after traveling to Indonesia. Based on the clinical features and a positive real-time polymerase chain reaction for dengue virus type 1, she was diagnosed with dengue fever. The patient developed dengue maculopathy mainly affecting the vision of her left eye. Abnormalities on a multifocal electroretinogram showed bilateral involvement. Results: As there is no proven treatment for dengue maculopathy, the patient opted for observation. Her vision returned to normal within 3 weeks. Conclusion: Dengue maculopathy can cause severe visual loss and may resolve without treatment.

  7. Clinical score to differentiate scrub typhus and dengue: A tool to differentiate scrub typhus and dengue

    Directory of Open Access Journals (Sweden)

    Shubhanker Mitra

    2017-01-01

    Full Text Available Background: Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. Materials and Methods: We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Results: Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%, total white blood cell count (7000 cells/cumm, hemoglobin (≤14 and >14 g/dL, total bilirubin (200 and ≥200 IU/dL, and altered sensorium (present or absent. Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval for model 2 was 0.84 (0.79–0.89. At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. Conclusion: In areas of high burden of ST and dengue, model 2 (the “clinical score to differentiate scrub typhus and dengue fever” is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

  8. Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

    Science.gov (United States)

    Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

    2017-01-01

    Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

  9. Evaluation of Internet-based dengue query data: Google Dengue Trends.

    Directory of Open Access Journals (Sweden)

    Rebecca Tave Gluskin

    2014-02-01

    Full Text Available Dengue is a common and growing problem worldwide, with an estimated 70-140 million cases per year. Traditional, healthcare-based, government-implemented dengue surveillance is resource intensive and slow. As global Internet use has increased, novel, Internet-based disease monitoring tools have emerged. Google Dengue Trends (GDT uses near real-time search query data to create an index of dengue incidence that is a linear proxy for traditional surveillance. Studies have shown that GDT correlates highly with dengue incidence in multiple countries on a large spatial scale. This study addresses the heterogeneity of GDT at smaller spatial scales, assessing its accuracy at the state-level in Mexico and identifying factors that are associated with its accuracy. We used Pearson correlation to estimate the association between GDT and traditional dengue surveillance data for Mexico at the national level and for 17 Mexican states. Nationally, GDT captured approximately 83% of the variability in reported cases over the 9 study years. The correlation between GDT and reported cases varied from state to state, capturing anywhere from 1% of the variability in Baja California to 88% in Chiapas, with higher accuracy in states with higher dengue average annual incidence. A model including annual average maximum temperature, precipitation, and their interaction accounted for 81% of the variability in GDT accuracy between states. This climate model was the best indicator of GDT accuracy, suggesting that GDT works best in areas with intense transmission, particularly where local climate is well suited for transmission. Internet accessibility (average ∼ 36% did not appear to affect GDT accuracy. While GDT seems to be a less robust indicator of local transmission in areas of low incidence and unfavorable climate, it may indicate cases among travelers in those areas. Identifying the strengths and limitations of novel surveillance is critical for these types of data to

  10. Dengue surveillance in Veterans Affairs healthcare facilities, 2007-2010.

    Directory of Open Access Journals (Sweden)

    Patricia L Schirmer

    Full Text Available BACKGROUND: Although dengue is endemic in Puerto Rico (PR, 2007 and 2010 were recognized as epidemic years. In the continental United States (US, outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL, in 2009-2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA healthcare facilities and then to clinically compare dengue cases in Veterans presenting for care in PR and in FL. METHODOLOGY: Outpatient encounters from 1/2007-12/2010 and inpatient admissions (only available from 10/2009-12/2010 with dengue diagnostic codes at all VA facilities were identified using VA's Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE. Additional case sources included VA data from Centers for Disease Control and Prevention BioSense and VA infection preventionists. Case reviews were performed. Categorical data was compared using Mantel-Haenszel or Fisher Exact tests and continuous variables using t-tests. Dengue case residence was mapped. FINDINGS: Two hundred eighty-eight and 21 PR and FL dengue cases respectively were identified. Of 21 FL cases, 12 were exposed in Key West and 9 were imported. During epidemic years, FL cases had significantly increased dengue testing and intensive care admissions, but lower hospitalization rates and headache or eye pain symptoms compared to PR cases. There were no significant differences in clinical symptoms, laboratory abnormalities or outcomes between epidemic and non-epidemic year cases in FL and PR. Confirmed/probable cases were significantly more likely to be hospitalized and have thrombocytopenia or leukopenia compared to suspected cases. CONCLUSIONS: Dengue re-introduction in the continental US warrants increased dengue surveillance and education in VA. Throughout VA, under-testing of suspected cases highlights the need to

  11. Dengue Contingency Planning: From Research to Policy and Practice

    Science.gov (United States)

    Runge-Ranzinger, Silvia; Kroeger, Axel; Olliaro, Piero; McCall, Philip J.; Sánchez Tejeda, Gustavo; Lloyd, Linda S.; Hakim, Lokman; Bowman, Leigh R.; Horstick, Olaf; Coelho, Giovanini

    2016-01-01

    Background Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. Methodology/Principal findings Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. Conclusions/Significance Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak

  12. Dengue, zika, chikungunya and the development of vaccines

    OpenAIRE

    Isabel N. Kantor

    2018-01-01

    Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjec...

  13. VAKSIN DENGUE DAN PERKEMBANGANNYA SAAT INI DAN DI MASA MENDATANG

    Directory of Open Access Journals (Sweden)

    Triwibowo Ambar Garjito

    2012-09-01

    Full Text Available Dengue virus merupakan salah satu virus anggota dari famili Flaviviridae yang sejak tahun 1956 telah dikenal dapat menimbulkan demam dengue maupun demam berdarah dengue (DBD. Penyakit yang ditularkan oleh nyamuk Aedes aegypti ini diperkirakan telah menjangkiti pada selatar 50-100 juta manusia dengan 500.000 kasus di antaranya dalam manifestasi yang ganas yang dikenal sebagai dengue haemorrhagic fever dan dengue shock syndrome dan 25.000 di antaranya berakibat fatal (meninggal. Saat ini pengembangan vaksin merupakan salah satu solusi yang diharapkan dapat menekan penyebaran penyakit tersebut. E (envelope merupakan salah satu bagian dari protein struktural virus yang sangat penting dalam pengembangan vaksin, yaitu sebagai badan yang memproduksi antibodi netralisasi untuk protein. Non-struktural protein l juga telah diketahui sebagai salah satu komponen penting dalam pengembangan vaksin oleh karena kemampuannya untuk dapat diekspresi pada permukaan sel yang diinfeksi yang dapat menjadi target untuk immune cytolisis. Ada dua pendekatan yang digunakan dalam memproduksi suatu vaksin dengue, yaitu: a. Vaksin hidup yang telah dilemahkan (live attenuated vaccine: b. Vaksin hasil rekayasa (engineered vaccine. Penelitian terhadap vaksin DENV baik rekombinan maupun non-rekombinan yang didasarkan pada uji virus telah dilakukan secara terus-menerus baik pada monyet dan manusia. Sampai saat ini telah dikembangkan sejumlah kandidat vaksin DENV yang berdasar pada tetravalent virus dengue, yaitu a. vaksin konvensional, b. vaksin dengue rekombinan berdasar pada flavivirus, c. vaksin intertypic chimeric, d. vaksin chimerivac, e. vaksin dengue rekombinan menggunakan vector non-ftavivirus dan f. vector adenovirus. Namun demikian, sampai sekarang belum ada vaksin yang siap digunakan untuk menangkal infeksi ke empat serotype virus dengue, sehingga masih diharapkan untuk pengembangan virus lebih lanjut.   Kata kunci: Aedes aegypti, dengue virus, vaksin dengue.

  14. Dengue fever as a cause of hemophagocytic lymphohistiocytosis

    OpenAIRE

    Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, D?bora Morais; Hirose, Maki; Ferronato, Angela Esp?sito; Pastorino, Ant?nio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias

    2015-01-01

    Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, pro...

  15. Imported dengue virus serotype 1 from Madeira to Finland 2012.

    Science.gov (United States)

    Huhtamo, E; Korhonen, Em; Vapalahti, O

    2013-02-21

    Imported dengue cases originating from the Madeiran outbreak are increasingly reported. In 2012 five Finnish travellers returning from Madeira were diagnosed with dengue fever. Viral sequence data was obtained from two patients. The partial C-preM sequences (399 and 396 bp respectively) were found similar to that of an autochthonous case from Madeira. The partial E-gene sequence (933 bp) which was identical among the two patients grouped phylogenetically with South American strains of dengue virus serotype 1.

  16. Dengue hemorrhagic fever and acute hepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Maria Paula Gomes Mourão

    Full Text Available Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  17. Dengue hemorrhagic fever and acute hepatitis: a case report.

    Science.gov (United States)

    Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães de; Bastos, Michele de Souza; Albuquerque, Bernardino Cláudio de; Alecrim, Wilson Duarte

    2004-12-01

    Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  18. Investigational drugs in early development for treating dengue infection.

    Science.gov (United States)

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2016-09-01

    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  19. Prevention and Control Strategies to Counter Dengue Virus Infection.

    Science.gov (United States)

    Rather, Irfan A; Parray, Hilal A; Lone, Jameel B; Paek, Woon K; Lim, Jeongheui; Bajpai, Vivek K; Park, Yong-Ha

    2017-01-01

    Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  20. Prevention and Control Strategies to Counter Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Irfan A. Rather

    2017-07-01

    Full Text Available Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  1. The 2012 dengue outbreak in Madeira: exploring the origins.

    Science.gov (United States)

    Wilder-Smith, A; Quam, M; Sessions, O; Rocklov, J; Liu-Helmersson, J; Franco, L; Khan, K

    2014-02-27

    In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

  2. Dengue fever in the San Juan Bay Estuary: Evaluating the ...

    Science.gov (United States)

    Dengue is transmitted by Aedes aegypti, a species that thrives in cities. Here we ask which elements within the urban environment could be managed to reduce the potential for Dengue occurrence. In particular, we study the potential of wetlands in the SJBE to buffer from vector proliferation. Wetlands provide ecosystem services such as heat and water hazard mitigation, water purification and habitat for a diversity of species, all of which are factors that have been shown to affect Dengue vectors. As such, we hypothesize that within coastal neighborhoods in the SJBE wetlands, ecosystem services lead to lower Dengue occurrence. We test this hypothesis using Dengue data from 2010-2013, which includes the largest epidemic in PR history. Our analytical model includes relevant socio-economic factors and environmental controls that may also affect Dengue dynamics. Results indicated a negative effect of neighborhood mangrove cover and a positive effect of percent flood area on Dengue prevalence. Moreover, heat hazards were positively correlated with dengue prevalence and negatively correlated with neighborhood mangrove cover. Dengue prevalence did not correlate with herbaceous wetlands, or with the ecosystem services of water quality or vertebrate species richness. Mosquito borne diseases are an increasingly important health concern, which pose great challenges for safe and sustainable control and eradication. This reality calls for management approaches that consider m

  3. A model of immunomodulatory for dengue infection mm

    Science.gov (United States)

    Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

    2018-03-01

    An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

  4. Spectrum of findings on magnetic resonance imaging of the brain in patients with neurological manifestations of dengue fever

    Directory of Open Access Journals (Sweden)

    Tejeshwar Singh Jugpal

    Full Text Available Abstract Objective: To describe the spectrum of magnetic resonance imaging (MRI findings in patients with neurological manifestations of dengue. Materials and Methods: We included nine patients with dengue fever (three females and six males; age range, 9–30 years, all of whom presented with neurological manifestations. The MRI examinations, performed in 1.5 T or 3 T scanners, included T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR sequences. Diffusion-weighted imaging with apparent diffusion coefficient mapping was also employed. Fast low-angle shot and susceptibility-weighted gradient-recalled echo sequences, as well as contrast-enhanced T1-weighted scans, were also obtained in order to assess parenchymal enhancement. MRI scans were analyzed for lesion distribution and imaging features. Results: All patients showed areas of altered signal intensity that appeared as hyperintensity on T2-weighted and FLAIR sequences. The most commonly affected site was the basal ganglia-thalamus complex. Other affected sites were the cerebellum, cerebral cortex, white matter, and brainstem. In all cases, we observed patchy areas of restricted diffusion and focal areas of hemorrhage. Conclusion: Dengue encephalitis commonly affects the basal ganglia, thalamus, cerebellum, cerebral cortex, and white matter. Therefore, MRI should be an indispensable part of the evaluation of patients with neurological complications of dengue fever.

  5. MORBIMORTALIDADE DA DENGUE EM IDOSOS NO BRASIL - DENGUE MORBIDITY AND MORTALITY IN ELDERLY IN BRAZIL

    Directory of Open Access Journals (Sweden)

    Annah Rachel Graciano

    2017-07-01

    Full Text Available Objective: To determine the prevalence and specific dengue coefficients of mortality in Brazil in the elderly population correlating the rates by male and female. Methods: Analytical ecological study with temporal trend of design. It was used as data sources Sistema de Informação Hospitalar, Sistema de Informação de Mortalidade and Instituto Brasileiro de Geografia e Estatística. The population corresponded to the elderly aged between 60 years to 100 attended at Brazilian public health system whom were diagnosed with dengue between 2008 and 2015. Results: The prevalence rates did not change in the general population between the years 2008 and 2015. There was a significant increase in the number of deaths from dengue. In the elderly group, the prevalence increased substantially, and the specific mortality analysis in this group showed higher values than the mortality of the general population affected by dengue. Conclusions: It is very important to underline studies on the involvement of dengue in elderly groups for the development of public politics and the creation of specific protocols for the diagnosis and treatment in that age group, considering the lack of scientific evidence to entail proper conduct in handling such patients

  6. Clinical profile and warning sign finding in children with severe dengue and non-severe dengue

    Science.gov (United States)

    Adam, A. S.; Pasaribu, S.; Wijaya, H.; Pasaribu, A. P.

    2018-03-01

    Dengue fever is one of the most important emerging vector-borne viral diseases. Approximately 500,000 out of 100 million cases develop to severe dengue infection. Patient with severe dengue (SD) can be predicted by clinical profile, laboratory and warning sign which could be saved by early interventions.This was a retrospective descriptive-analytic study to investigate clinical manifestations, laboratory and warning signs ofchildren with dengue infection in Haji Adam Malik hospital during January 2014–May 2016. Through medical records, we had selected 140 cases which fulfilled research criteria.Cases were classified as SD (n=28) and NSD (n=112). Most common clinical manifestations for NSD were abdominal pain (39.3%), myalgia (39.3%), headache (37.1%), mucosal bleeding (36.4%) while for SD were shock (15.7%), mucosal bleeding (15.7%), clinical fluid accumulation (15%), shortness of breath (14.3%). SGPT >1000IU/L (5 cases), SGOT >1000IU/L (9 cases), PT (10 cases) and aPTT (16 cases) were abnormal in SD. Severe dengue was frequently found in the range of white cell count 1000-4000/L and platelet count 20,000-50,000mm/uL. Clinical manifestations, warning sign, and laboratoryfinding, were different between SD and NSD.

  7. Factors affecting dengue prevention practices: nationwide survey of the Malaysian public.

    Directory of Open Access Journals (Sweden)

    Li Ping Wong

    Full Text Available Efforts to stamp dengue in many dengue endemic countries has met little success. There is a need to re-examine and understand how the public at large view the dengue prevention efforts. This study aimed to examine the demographic factors, theoretical constructs of the Health Belief Model and knowledge about dengue and how these influence the practice of dengue prevention.A national telephone survey was carried out with 2,512 individuals of the Malaysian public aged 18-60 years.The majority (73% of the Malaysian public had a total dengue prevention score of 51-100 (of a possible score of 1-100. Multivariate analysis suggests significant correlates of higher dengue prevention practices with demographic background, perception of susceptibility to dengue, perceived density of mosquitoes in the neighbourhood and knowledge about dengue. Households of lower income of which the majority (40.7% were from the rural areas, were associated with the highest odds [OR = 1.33; 95%CI = 1.09-1.67; p = 0.004] of dengue prevention. Dengue prevention practices were also less likely to be undertaken in neighbourhoods where the responders perceived there is no and/or low density of mosquitoes. Dengue prevention practices are also less likely to be practiced by skilled workers [OR = 0.78; 95%CI = 0.63-0.95; p = 0.029] compared to those unemployed. Higher perceived susceptibility to dengue was associated with higher dengue prevention practices and participants with higher dengue knowledge were found to have a higher level of involvement in dengue prevention practices.Results from the study suggest that in formulating approaches to contain dengue, strategies should be developed to cultivate dengue prevention practices among urban population and target areas with low density of mosquitoes where public perceived a less likely chance of getting dengue. Dengue prevention campaigns should focus on messages highlighting the risk of contracting dengue and education to increase

  8. Seroprevalence of dengue among healthy adults in a rural community in Southern Malaysia: a pilot study.

    Science.gov (United States)

    Dhanoa, Amreeta; Hassan, Sharifah Syed; Jahan, Nowrozy Kamar; Reidpath, Daniel D; Fatt, Quek Kia; Ahmad, Mohtar Pungut; Meng, Cheong Yuet; Ming, Lau Wee; Zain, Anuar Zaini; Phipps, Maude Elvira; Othman, Iekhsan; Rabu, Aman Bin; Sirajudeen, Rowther; Fatan, Ahmad Abdul Basitz Ahmad; Ghafar, Faidzal Adlee; Ahmad, Hamdan Bin; Allotey, Pascale

    2018-01-16

    exposure to dengue. The finding of a high proportion of unreported cases possibly due to subclinical infections underscores the need for enhanced surveillance and control methods. This finding also has implications for measuring disease burden, understanding transmission dynamics, and hypothesizing effects on DENV vaccine efficacy and uptake.

  9. Fundamental studies on ADCC (antibody-dependent cell-mediated cytotoxicity) of human peripheral blood leukocytes using sheep red blood cells as target cells, and the effect of erythrophagocytosis

    International Nuclear Information System (INIS)

    Ichikawa, Yukinobu; Takaya, Masatoshi; Arimori, Shigeru

    1979-01-01

    We investigated antibody-dependent cell-mediated cytotoxicity (ADCC) of human peripheral blood leukocytes by using 51 Cr-labelled sheep red blood cells (SRBC) as target cells and anti-SRBC rabbit antibody. Lysis of SRBC was mediated by either human peripheral lymphoid cells or phagocytes (Monocytes and granulocytes). SRBC were useful as target cells in ADCC assay against human lymphoid cells, since decreased cytotoxic activity of phagocyte-contaminated crude lymphocyte fraction was recovered by elimination of contaminating phagocytes. The monocytes inhibited ADCC of lymphoid cells through phagocytosis of SRBC. This assay system may be useful for estimating not only Fc receptor-mediated cytotoxicity but also Fc receptor-mediated phagocytic activity of human peripheral blood leukocytes. (author)

  10. Characterization of Dengue Virus Resistance to Brequinar in Cell Culture▿

    Science.gov (United States)

    Qing, Min; Zou, Gang; Wang, Qing-Yin; Xu, Hao Ying; Dong, Hongping; Yuan, Zhiming; Shi, Pei-Yong

    2010-01-01

    Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release. PMID:20606073

  11. Epidemiology of dengue: past, present and future prospects

    Directory of Open Access Journals (Sweden)

    Murray NE

    2013-08-01

    Full Text Available Natasha Evelyn Anne Murray,1,2 Mikkel B Quam,1 Annelies Wilder-Smith1,31Institute of Public Health, University of Heidelberg, Heidelberg, Germany; 2Population Health, Waikato District Health Board, Hamilton, New Zealand; 3Lee Kong Chian School of Medicine, Nanyang Technological University, SingaporeAbstract: Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265–420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue

  12. Evaluation of concurrent malaria and dengue infections among febrile patients

    Directory of Open Access Journals (Sweden)

    Parul D Shah

    2017-01-01

    Full Text Available Context: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. Aims: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. Setting and Design: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. Subjects and Methods: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Results: Only 10.27% (859 patients with fever were tested positive for dengue and 5.1% (434 were tested positive for malaria. 3.14% (27 dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10, haemorrhagic manifestations 18.51% (5 and kidney failure 3.7% (1, haemoglobin <12 g/dl 100% (27 and thrombocytopenia (platelet count <150,000/cmm 96.29% (26 were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. Conclusion: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.

  13. Sensorineural hearing loss in hemorrhagic dengue?

    Directory of Open Access Journals (Sweden)

    Bruna Natália Freire Ribeiro

    2015-01-01

    Discussion and conclusion: This is the first case report that brings together DHF and sudden hearing loss. In the development of this case no other cause to sudden hearing loss was found and the correlation between dengue and hearing loss was questioned. In the literature review was found that some viruses, as mumps virus, varicella-zoster virus and HSV-1 and HSV-2 are related to sudden hearing loss, all of them fit in the viral theory. Besides the viral theory of sudden hearing loss, there is the vascular theory that is the occlusion of the end artery that supplies the cochlea. DHF has a vascular commitment, and the hypothesis of a vascular cause could be elicited in this case. Many studies in this area are needed and this article has the objective of elicit the discussion about the subject. Could dengue be associated with sensorineural hearing loss?

  14. Desarrollo de agentes inmunizantes contra el dengue

    Directory of Open Access Journals (Sweden)

    Francisco J. López Antuñano

    2000-05-01

    Full Text Available El complejo de los cuatro flavivirus del dengue es transmitido principalmente por el mosquito Aedes aegypti. Se han atribuido epidemias a la actividad de A. albopictus, A. polynesiensis y a varias especies del complejo A. scutellaris. Los factores de riesgo que determinan la probabilidad de enfermar o morir por dengue están relacionados tanto con el huésped (características genéticas, estado inmunitario, forma de vida y condiciones de salud, saneamiento básico de la vivienda y abastecimiento de agua potable como con el virus (variabilidad genética de cepas entre y dentro de los serotipos, diferente capacidad patógena y distribución geográfica. A pesar de la falta de conocimiento sobre la inmunobiopatología del dengue, se han hecho importantes avances para conseguir una respuesta inmunitaria protectora con virus atenuados y con antígenos obtenidos por medio de tecnologías recombinantes. Desde los años 40, se ha intentado desarrollar vacunas contra el dengue. La inmunidad que se adquiere por infección natural es específica para cada serotipo y se han documentado infecciones por tres serotipos diferentes en la misma persona, por lo que probablemente sea necesaria una vacuna tetravalente. En voluntarios se han probado vacunas contra los cuatro serotipos que han sido inmunógenas y seguras. Aunque las vacunas con virus atenuados son prometedoras, son necesarios nuevos estudios sobre su eficacia y seguridad. Actualmente están en curso estudios para producir vacunas contra el virus del dengue mediante tecnologías de ADN recombinante y otras técnicas de biología molecular, utilizando como antígenos proteínas estructurales (principalmente la glicoproteína E y no estructurales. Con el mismo propósito se han usado varios vectores de expresión, como Escherichia coli, baculovirus, virus de la vacuna y virus de la fiebre amarilla. Lamentablemente, no se han obtenido resultados satisfactorios en el hombre. La necesidad de desarrollar

  15. The Medicinal Chemistry of Dengue Virus.

    Science.gov (United States)

    Behnam, Mira A M; Nitsche, Christoph; Boldescu, Veaceslav; Klein, Christian D

    2016-06-23

    The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry or structure-activity relationship (SAR), or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated toward other emerging flaviviral infections, such as West Nile virus. Therefore, this perspective, although not aimed at flaviviruses in general, should also be able to provide an overview of the medicinal chemistry of these closely related infectious agents.

  16. Dengue Virus Glycosylation: What Do We Know?

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    Sally S. L. Yap

    2017-07-01

    Full Text Available In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E and non-structural protein 1 (NS1 are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

  17. 75 FR 6211 - Prospective Grant of Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine...

    Science.gov (United States)

    2010-02-08

    ... Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,2,3, and 4 AGENCY: National Institutes of Health, Public Health...., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses''-- European Patent...

  18. Dengue risk factors and community participation in Binh Thuan Province, Vietnam, a household survey

    NARCIS (Netherlands)

    Phuong, Hoang Lan; de Vries, Peter J.; Boonshuyar, Chaweewon; Binh, Tran Q.; Nam, Nguyen V.; Kager, Piet A.

    2008-01-01

    To look for risk factors for dengue and community participation in dengue control in Binh Thuan Province, Vietnam, three communes with a low incidence of dengue and three with a high incidence, in Binh Thuan Province, were compared. Knowledge, perception and preventive practice of dengue were

  19. Pharmacological intervention for dengue virus infection.

    Science.gov (United States)

    Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

    2017-04-01

    Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. "We need people to collaborate together against this disease": A qualitative exploration of perceptions of dengue fever control in caregivers' of children under 5 years, in the Peruvian Amazon.

    Science.gov (United States)

    Frank, Amy L; Beales, Emily R; de Wildt, Gilles; Meza Sanchez, Graciela; Jones, Laura L

    2017-09-01

    Dengue Fever presents a significant and growing burden of disease to endemic countries, where children are at particular risk. Worldwide, no effective anti-viral treatment has been identified, thus vector control is key for disease prevention, particularly in Peru where no vaccine is currently available. This qualitative study aimed to explore the perceptions of dengue control in caregivers' of children under 5 years in Peru, to help direct future mosquito control programmes and strategy. Eighteen semi-structured interviews were conducted in one health centre in Iquitos, Peru. Interviews were audio-recorded, transcribed and translated by an independent translator. Data were analysed using an inductive thematic approach. Three core analytic themes were interpreted: (1) awareness of dengue and its control, (2) perceived susceptibility of children, rural riverside communities and city inhabitants, and (3) perceived responsibility of vector control. Participants were aware of dengue symptoms, transmission and larvae eradication strategies. Misconceptions about the day-time biting behaviour of the Aedes aegypti mosquito and confusion with other mosquito-borne diseases influenced preventative practice. Community-wide lack of cooperation was recognised as a key barrier. This was strengthened by attitudes that the government or health centre were responsible for dengue control and a belief that the disease cannot be prevented through individual actions. Participants felt powerless to prevent dengue due to assumed inevitability of infection and lack of faith in preventative practices. However, children and rural communities were believed to be most vulnerable. Perceptions of dengue control amongst caregivers to under 5's were important in shaping their likelihood to participate in preventative practices. There is a need to address the perceived lack of community cooperation through strategies creating a sense of ownership of community control and enhancing social

  1. Challenges in dengue fever in the elderly: atypical presentation and risk of severe dengue and hospital-acquired infection [corrected].

    Directory of Open Access Journals (Sweden)

    Emily K Rowe

    2014-04-01

    Full Text Available BACKGROUND/METHODS: To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO dengue classification and outcomes between adult (<60 and elderly (≥60 dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included. RESULTS: Of the 6989 cases, 295 (4.4% were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF (29.2% vs. 21.4% and severe dengue (SD (20.3% vs. 14.6% (p<0.05. Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4% (p = 0.014, but not WHO 2009 probable dengue (75.3% vs. 71.5%. Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006 and malaise/lethargy (p = 0.033 while the adults had significantly more mucosal bleeding (p<0.001. Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days, and suffered more pneumonia (3.8% vs. 0.7% and urinary infection (1.9% vs. 0.3% (p = 0.003. Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37-2.88, critical illness (aOR 5.13, 95%CI 2.59-9.75, HAI (aOR 12.06, 95%CI 7.39-19.9, Charlson score (aOR 6.9, 95%CI 2.02-22.56 and severe dengue (DHF/dengue shock syndrome/SD (aOR 2.24, 95%CI 1.83-2.74. CONCLUSION: Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside from dengue

  2. Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study.

    Science.gov (United States)

    Suppiah, Jeyanthi; Chan, Shie-Yien; Ng, Min-Wern; Khaw, Yam-Sim; Ching, Siew-Mooi; Mat-Nor, Lailatul Akmar; Ahmad-Najimudin, Naematul Ain; Chee, Hui-Yee

    2017-06-28

    Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection. Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined. The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study. The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

  3. Knowledge of dengue among students in Universiti Sultan Zainal ...

    African Journals Online (AJOL)

    Reducing the vector population not only organization responsible, individual itself plays as important role in dengue prevention and control. Upon the understanding of the value of baseline data, a cross-sectional study was carried out in the dengue hotspot areas in Universiti Sultan Zainal Abidin (UniSZA). The study results ...

  4. Dengue in the United States of America: A Worsening Scenario?

    Directory of Open Access Journals (Sweden)

    Germán Añez

    2013-01-01

    Full Text Available Dengue is a febrile illness caused by any of the four dengue virus types (DENV-1 to -4, genus Flavivirus, family Flaviviridae mainly transmitted by the mosquito Aedes aegypti. DENV can be transmitted by blood transfusion. Dengue has been historically present in the continental United States (US, in the state of Hawaii, and in the US insular territories in the Caribbean and the Pacific. During the second half of the 20th century, most of the cases reported in the US were imported cases brought to the country by travelers. Since 2009, cases of autochthonous dengue have been recognized in the state of Florida after 75 years of absence, followed by intensification of transmission in endemic places including the US territories of US Virgin Islands and Puerto Rico, which experienced a large dengue epidemic in 2010. The widespread distribution of dengue mosquito vectors, deficient mosquito control measures and increased frequency of DENV-infected visitors to the US coming from dengue-endemic locations or places experiencing epidemics appear to be jointly responsible for the emergence and reemergence of dengue in the US and its territories.

  5. Emergence of Dengue virus serotype 3 on Mayotte Island, Indian ...

    African Journals Online (AJOL)

    A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of ...

  6. Isolation of Ancestral Sylvatic Dengue Virus Type 1, Malaysia

    Science.gov (United States)

    Teoh, Boon-Teong; Sam, Sing-Sin; Abd-Jamil, Juraina

    2010-01-01

    Ancestral sylvatic dengue virus type 1, which was isolated from a monkey in 1972, was isolated from a patient with dengue fever in Malaysia. The virus is neutralized by serum of patients with endemic DENV-1 infection. Rare isolation of this virus suggests a limited spillover infection from an otherwise restricted sylvatic cycle. PMID:21029545

  7. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever.

    NARCIS (Netherlands)

    Gorp, E. van; Setiati, T.E.; Mairuhu, A.T.; Suharti, C.; Cate, H.H.; Dolmans, W.M.V.; Meer, J.W.M. van der; Hack, C.E.; Brandjes, D.P.

    2002-01-01

    The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was

  8. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever

    NARCIS (Netherlands)

    van Gorp, Eric C. M.; Setiati, Tatty E.; Mairuhu, Albert T. A.; Suharti, Catharina; Cate Ht, Hugo ten; Dolmans, Wil M. V.; van der Meer, Jos W. M.; Hack, C. Erik; Brandjes, Dees P. M.

    2002-01-01

    The mechanisms contributing to bleeding complications in dengue hemorrhagic fever were studied by investigating the pattern of activation of the coagulation and fibrinolytic systems in 50 children with severe dengue hemorrhagic fever. Thirteen patients (26%) died, and activation of coagulation was

  9. Dengue Outbreak in Hadramout, Yemen, 2010: An Epidemiological Perspective

    Science.gov (United States)

    Ghouth, Abdulla Salim Bin; Amarasinghe, Ananda; Letson, G. William

    2012-01-01

    We analyzed surveillance data of a dengue outbreak (2010) reported to the Hadramout Health Office (Yemen) and retrospectively analyzed dengue-related epidemiological and entomological events reported in Hadramout from 2005 to 2009. A total of 630 immunoglobulin M (IgM) -confirmed dengue cases of 982 febrile cases was reported during the period from February to June of 2010; 12 cases died, giving case fatality a rate of 1.9%. Among febrile cases, the highest proportion of dengue cases (37.3%) was reported in the 15- to 24-year-old age group. The overall attack rate was 0.89/1,000. The average number of cases reported by month over the preceding 5-year period compared with the 2010 data is consistent with endemicity of dengue in the region and supports epidemic designation for the dengue activity in 2010. Recognition of endemic dengue transmission and potential for substantial dengue epidemics highlight the need for consistent laboratory-based surveillance that can support prevention and control activities accordingly. PMID:22665621

  10. Projections of increased and decreased dengue incidence under climate change.

    Science.gov (United States)

    Williams, C R; Mincham, G; Faddy, H; Viennet, E; Ritchie, S A; Harley, D

    2016-10-01

    Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

  11. Dengue Knowledge and Preventive Practices in Iquitos, Peru.

    Science.gov (United States)

    Paz-Soldán, Valerie A; Morrison, Amy C; Cordova Lopez, Jhonny J; Lenhart, Audrey; Scott, Thomas W; Elder, John P; Sihuincha, Moises; Kochel, Tadeusz J; Halsey, Eric S; Astete, Helvio; McCall, Philip J

    2015-12-01

    As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved. © The American Society of Tropical Medicine and Hygiene.

  12. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  13. Immune Activation in the Pathogenesis of Dengue Virus Infection

    NARCIS (Netherlands)

    C.A.M. van de Weg (Cornelia A.M.)

    2014-01-01

    markdownabstract__Abstract__ Dengue virus (DENV) is a positive-stranded RNA virus and belongs to the Flaviviridae family. The virus is transmitted by the bite of an infected Aedes-mosquito and circulates in tropical and subtropical areas around the world. The incidence of dengue has risen

  14. Dengue virus exposure among blood donors in Ghana | Narkwa ...

    African Journals Online (AJOL)

    Dengue is an urban arbovirus whose aetiologic agent is the flavivirus with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. Ghana is endemic for Aedes aegypti mosquitoes and probably dengue viruses. Due to limited data ...

  15. Deranged liver among Sudanese patients with dengue virus ...

    African Journals Online (AJOL)

    Background: Deranged liver is a well-recognized feature of dengue infection, often demonstrated by coagulopathy and mild to moderate increase in transaminase levels although jaundice and fulminant hepatic failure are generally uncommon. Objective: This study aimed to evaluate the hepatic effect of dengue fever ...

  16. Ludwig's angina after severe thrombocytopenic purpura associated with dengue fever

    Directory of Open Access Journals (Sweden)

    Maria Antonia Campos

    2014-01-01

    Full Text Available Here, we report a case of Ludwig's angina, which required surgery because of toothache. The patient had dengue and severe thrombocytopenia as confirmed by clinical and laboratory diagnoses. However, dengue is not included among the predisposing factors for Ludwig's angina.

  17. Socio-demographic determinants of dengue infection during an ...

    African Journals Online (AJOL)

    Dell

    4Southern African Centre for Infectious Disease Surveillance, Africa Centre of Excellence for Infectious Diseases of. Humans and ..... Erlanger, T.E., Keiser, J. & Utzinger, J. (2008) Effect of dengue vector control interventions on ... Dengue fever among hospitalized febrile patients in northern Tanzania. American Journal of.

  18. Genetic analysis of imported dengue virus strains by Iranian travelers

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    Nariman Shahhosseini

    2016-11-01

    Full Text Available Dengue virus sequences used in this study were obtained from two Iranian patients who were both with a history of traveling to Malaysia. The maximum likelihood phylogenetic tree demonstrated that two sequences were grouped into dengue virus 1. Specifically, strains IranDF1 and Iran-DF2 clustered in genotype I and III, respectively.

  19. Climate Variability, Social Change and Dengue in Bangladesh ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Researchers will carry out a serological study in nine city wards in Dhaka with different levels of dengue virus transmission; a clinical study of suspected cases of dengue in two hospitals; entomological surveys in the nine wards already mentioned; and an ethnographic study in three wards to examine the social and ...

  20. Dengue as a cause of acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, H.L.; de Vries, P.J.; Nga, T.T.T.; Giao, P.T.; Hung, L.Q.; Binh, T.Q.; Nam, N.V.; Nagelkerke, N.; Kager, P.A.

    2006-01-01

    Background: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh

  1. Dengue fever associated with acute scrotal oedema: two case reports

    International Nuclear Information System (INIS)

    Shamim, M.; Naqvi, S.Z.G.

    2011-01-01

    Scrotal oedema associated with dengue fever is a rare and self limiting condition resolving in a few days without any complication or sequelae. This is a report of two cases of dengue fever associated with acute scrotal and penile oedema. (author)

  2. Dengue data and surveillance in Tanzania: a systematic literature review.

    Science.gov (United States)

    Ward, Tara; Samuel, Moody; Maoz, Dorit; Runge-Ranzinger, Silvia; Boyce, Ross; Toledo, Joao; Velayudhan, Raman; Horstick, Olaf

    2017-08-01

    Although there is evidence that dengue virus is circulating in Tanzania, the country lacks a dengue surveillance system. Consequently, the true estimate of dengue seroprevalence, as well as the incidence in the population, the frequency and magnitude of outbreaks is unknown. This study therefore sought to systematically review available dengue data from Tanzania. The systematic review was conducted and reported using the PRISMA tool. Five databases (PubMed, Embase, Web of Science, WHOLIS and Google Scholar) were searched for articles using various keywords on the illness, data and geographical location. Identified articles were assessed for inclusion based on predefined eligibility criteria. Data were extracted from included articles, analysed and reported. Based on the 10 seroprevalence studies in defined populations with estimates of acute confirmed infections that were included in the review, the estimated seroprevalence of past dengue infection in Tanzania ranged from 50.6% in a health facility-based study to 11% in a population-based study. Acute confirmed infections of dengue were estimated to be as high as 38.2% of suspected cases. Only one study reported on an outbreak. It is evident that dengue needs to become part of regular disease surveillance in Tanzania. Control measures need to be instituted with a focus on building human resource capacity and integrating dengue control measures in ongoing health programmes, for both preventive and curative interventions. Systematic reviews are valuable in assessing health issues when surveillance data are not available. © 2017 John Wiley & Sons Ltd.

  3. Dengue as a cause of acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, Hoang Lan; de Vries, Peter J.; Nga, Tran T. T.; Giao, Phan T.; Hung, Le Q.; Binh, Tran Q.; Nam, Nguyen V.; Nagelkerke, Nico; Kager, Piet A.

    2006-01-01

    BACKGROUND: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh

  4. Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2016-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. Otherwise, another nearby city, Tainan City, had reported the biggest outbreak in 2015. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  5. Climate Variability, Social Change and Dengue in Bangladesh ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Since the year 2000, the major cities of Bangladesh have experienced a resurgence of dengue. Dengue is a major public health concern because of its epidemic potential in any one year, and because of the limited understanding of disease transmission dynamics in the country. This project aims to advance knowledge on ...

  6. A thiophene-modified screen printed electrode for detection of dengue virus NS1 protein.

    Science.gov (United States)

    Silva, M M S; Dias, A C M S; Cordeiro, M T; Marques, E; Goulart, M O F; Dutra, R F

    2014-10-01

    A thiophene-modified screen printed electrode (SPE) for detection of the Dengue virus non-structural protein 1 (NS1), an important marker for acute phase diagnosis, is described. A sulfur-containing heterocyclic compound, the thiophene was incorporated to a carbon ink to prepare reproducible screen printed electrodes. After cured, the thiophene SPE was coated by gold nanoparticles conjugated to Protein A to form a nanostrutured surface. The Anti-NS1 antibodies immobilized via their Fc portions via Protein A, leaving their antigen specific sites free circumventing the problem of a random antibodies immobilization. Amperometric responses to the NS1 protein of dengue virus were obtained by cyclic voltammetries performed in presence of ferrocyanide/ferricyanide as redox probe. The calibration curve of immunosensor showed a linear response from 0.04 µg mL(-1) to 0.6 µg mL(-1) of NS1 with a good linear correlation (r=0.991, pink enhanced the electroanalytical properties of the SPEs, increasing their reproducibility and sensitivity. This point-of-care testing represents a great potential for use in epidemic situations, facilitating the early diagnosis in acute phase of dengue virus. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection.

    Science.gov (United States)

    Hosseini, Samira; Aeinehvand, Mohammad M; Uddin, Shah M; Benzina, Abderazak; Rothan, Hussin A; Yusof, Rohana; Koole, Leo H; Madou, Marc J; Djordjevic, Ivan; Ibrahim, Fatimah

    2015-11-09

    The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

  8. Patterned Array of Poly(ethylene glycol Silane Monolayer for Label-Free Detection of Dengue

    Directory of Open Access Journals (Sweden)

    Nor Zida Rosly

    2016-08-01

    Full Text Available In the present study, the construction of arrays on silicon for naked-eye detection of DNA dengue was demonstrated. The array was created by exposing a polyethylene glycol (PEG silane monolayer to 254 nm ultraviolet (UV light through a photomask. Formation of the PEG silane monolayer and photomodifed surface properties was thoroughly characterized by using atomic force microscopy (AFM, X-ray photoelectron spectroscopy (XPS, and contact angle measurements. The results of XPS confirmed that irradiation of ultraviolet (UV light generates an aldehyde functional group that offers conjugation sites of amino DNA probe for detection of a specific dengue virus target DNA. Employing a gold enhancement process after inducing the electrostatic interaction between positively charged gold nanoparticles and the negatively charged target DNA hybridized to the DNA capture probe allowed to visualize the array with naked eye. The developed arrays demonstrated excellent performance in diagnosis of dengue with a detection limit as low as 10 pM. The selectivity of DNA arrays was also examined using a single base mismatch and noncomplementary target DNA.

  9. Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Annie Elong Ngono

    2016-11-01

    Full Text Available Infection with one of the four dengue virus serotypes (DENV1-4 presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed “original antigenic sin,” secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response. The goal of our study was to compare the roles of serotype-specific and cross-reactive T cells in protection vs. pathogenesis during DENV infection in vivo. Specifically, we utilized IFN-α/βR−/− HLA*B0702 transgenic mice in the context of peptide vaccination with relevant human CD8 T cell epitopes. IFN-α/βR−/− HLA*B0702 transgenic mice were immunized with DENV serotype 2 (DENV2-specific epitopes or variants found in any of the other three serotypes (DENV1, DENV3 or DENV4, followed by challenge with DENV. Although cross-reactive T cell responses were lower than responses elicited by serotype-specific T cells, immunization with either serotype-specific or variant peptide epitopes enhanced viral clearance, demonstrating that both serotype-specific and cross-reactive T cells can contribute to protection in vivo against DENV infection.

  10. The Effect of Hydrocotyle sibthorpioides Lam. Extracts on In Vitro Dengue Replication

    Directory of Open Access Journals (Sweden)

    Fitrien Husin

    2015-01-01

    Full Text Available Objective. To investigate the potential effect of Hydrocotyle sibthorpioides Lam. (H. sibthorpioides extracts against in vitro dengue viral replication. Methods. The cytotoxicity of H. sibthorpioides was evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts of H. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay. Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells with H. sibthorpioides extract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells with H. sibthorpioides methanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication. Conclusion. H. sibthorpioides had variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties of H. sibthorpioides extracts on dengue virus.

  11. Findings at brain MRI in children with dengue fever and neurological symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Ruchi; Garg, Bhavya [Indraprastha Apollo Hospitals, Department of Radiodiagnosis, New Delhi (India)

    2016-01-15

    Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to DEN 4. There has been an increase in incidence of dengue infection in children in the tropics and subtropics. Dengue has a variable clinical presentation, with many patients being asymptomatic. Its clinical manifestations in children vary from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue shock syndrome. We describe MRI findings in children with neurological involvement including dengue encephalopathy, acute hypoxic injury and dengue encephalitis. Dengue encephalopathy is usually secondary to multisystem derangement such as shock, hepatitis, coagulopathy and concurrent bacterial infection and is relatively common. Dengue encephalitis from direct neuronal invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection. Clinical and laboratory findings as well as outcome do not necessarily correspond with brain MRI findings. (orig.)

  12. Findings at brain MRI in children with dengue fever and neurological symptoms

    International Nuclear Information System (INIS)

    Rastogi, Ruchi; Garg, Bhavya

    2016-01-01

    Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to DEN 4. There has been an increase in incidence of dengue infection in children in the tropics and subtropics. Dengue has a variable clinical presentation, with many patients being asymptomatic. Its clinical manifestations in children vary from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue shock syndrome. We describe MRI findings in children with neurological involvement including dengue encephalopathy, acute hypoxic injury and dengue encephalitis. Dengue encephalopathy is usually secondary to multisystem derangement such as shock, hepatitis, coagulopathy and concurrent bacterial infection and is relatively common. Dengue encephalitis from direct neuronal invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection. Clinical and laboratory findings as well as outcome do not necessarily correspond with brain MRI findings. (orig.)

  13. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

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    Ghazi A. Jamjoom

    2016-01-01

    Full Text Available Background Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. Methods Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. Results The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939 and 37% (68/184 in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1% reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others

  14. Desarrollo de agentes inmunizantes contra el dengue Development of immunizing agents against dengue

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    Francisco J. López Antuñano

    2000-05-01

    Full Text Available El complejo de los cuatro flavivirus del dengue es transmitido principalmente por el mosquito Aedes aegypti. Se han atribuido epidemias a la actividad de A. albopictus, A. polynesiensis y a varias especies del complejo A. scutellaris. Los factores de riesgo que determinan la probabilidad de enfermar o morir por dengue están relacionados tanto con el huésped (características genéticas, estado inmunitario, forma de vida y condiciones de salud, saneamiento básico de la vivienda y abastecimiento de agua potable como con el virus (variabilidad genética de cepas entre y dentro de los serotipos, diferente capacidad patógena y distribución geográfica. A pesar de la falta de conocimiento sobre la inmunobiopatología del dengue, se han hecho importantes avances para conseguir una respuesta inmunitaria protectora con virus atenuados y con antígenos obtenidos por medio de tecnologías recombinantes. Desde los años 40, se ha intentado desarrollar vacunas contra el dengue. La inmunidad que se adquiere por infección natural es específica para cada serotipo y se han documentado infecciones por tres serotipos diferentes en la misma persona, por lo que probablemente sea necesaria una vacuna tetravalente. En voluntarios se han probado vacunas contra los cuatro serotipos que han sido inmunógenas y seguras. Aunque las vacunas con virus atenuados son prometedoras, son necesarios nuevos estudios sobre su eficacia y seguridad. Actualmente están en curso estudios para producir vacunas contra el virus del dengue mediante tecnologías de ADN recombinante y otras técnicas de biología molecular, utilizando como antígenos proteínas estructurales (principalmente la glicoproteína E y no estructurales. Con el mismo propósito se han usado varios vectores de expresión, como Escherichia coli, baculovirus, virus de la vacuna y virus de la fiebre amarilla. Lamentablemente, no se han obtenido resultados satisfactorios en el hombre. La necesidad de desarrollar

  15. Population dynamics of Aedes aegypti and dengue as influenced by weather and human behavior in San Juan, Puerto Rico.

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    Roberto Barrera

    2011-12-01

    Full Text Available Previous studies on the influence of weather on Aedes aegypti dynamics in Puerto Rico suggested that rainfall was a significant driver of immature mosquito populations and dengue incidence, but mostly in the drier areas of the island. We conducted a longitudinal study of Ae. aegypti in two neighborhoods of the metropolitan area of San Juan city, Puerto Rico where rainfall is more uniformly distributed throughout the year. We assessed the impacts of rainfall, temperature, and human activities on the temporal dynamics of adult Ae. aegypti and oviposition. Changes in adult mosquitoes were monitored with BG-Sentinel traps and oviposition activity with CDC enhanced ovitraps. Pupal surveys were conducted during the drier and wetter parts of the year in both neighborhoods to determine the contribution of humans and rains to mosquito production. Mosquito dynamics in each neighborhood was compared with dengue incidence in their respective municipalities during the study. Our results showed that: 1. Most pupae were produced in containers managed by people, which explains the prevalence of adult mosquitoes at times when rainfall was scant; 2. Water meters were documented for the first time as productive habitats for Ae. aegypti; 3. Even though Puerto Rico has a reliable supply of tap water and an active tire recycling program, water storage containers and discarded tires were important mosquito producers; 4. Peaks in mosquito density preceded maximum dengue incidence; and 5. Ae. aegypti dynamics were driven by weather and human activity and oviposition was significantly correlated with dengue incidence.

  16. Population dynamics of Aedes aegypti and dengue as influenced by weather and human behavior in San Juan, Puerto Rico.

    Science.gov (United States)

    Barrera, Roberto; Amador, Manuel; MacKay, Andrew J

    2011-12-01

    Previous studies on the influence of weather on Aedes aegypti dynamics in Puerto Rico suggested that rainfall was a significant driver of immature mosquito populations and dengue incidence, but mostly in the drier areas of the island. We conducted a longitudinal study of Ae. aegypti in two neighborhoods of the metropolitan area of San Juan city, Puerto Rico where rainfall is more uniformly distributed throughout the year. We assessed the impacts of rainfall, temperature, and human activities on the temporal dynamics of adult Ae. aegypti and oviposition. Changes in adult mosquitoes were monitored with BG-Sentinel traps and oviposition activity with CDC enhanced ovitraps. Pupal surveys were conducted during the drier and wetter parts of the year in both neighborhoods to determine the contribution of humans and rains to mosquito production. Mosquito dynamics in each neighborhood was compared with dengue incidence in their respective municipalities during the study. Our results showed that: 1. Most pupae were produced in containers managed by people, which explains the prevalence of adult mosquitoes at times when rainfall was scant; 2. Water meters were documented for the first time as productive habitats for Ae. aegypti; 3. Even though Puerto Rico has a reliable supply of tap water and an active tire recycling program, water storage containers and discarded tires were important mosquito producers; 4. Peaks in mosquito density preceded maximum dengue incidence; and 5. Ae. aegypti dynamics were driven by weather and human activity and oviposition was significantly correlated with dengue incidence.

  17. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Clinical and laboratory factors associated with mortality in dengue.

    Science.gov (United States)

    Saroch, Atul; Arya, Vivek; Sinha, Nitin; Taneja, R S; Sahai, Pooja; Mahajan, R K

    2017-04-01

    Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the 172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum transaminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise multivariate logistic regression, altered sensorium ( P = 0.006) and hypoalbuminemia ( P = 0.013) were identified as independent predictors of mortality in dengue. Identification of these parameters early in the course of disease should prompt intensification of treatment in dengue cases.

  19. Environmentally-driven ensemble forecasts of dengue fever

    Science.gov (United States)

    Yamana, T. K.; Shaman, J. L.

    2017-12-01

    Dengue fever is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas where dengue is found, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission remains a significant public health challenge. Recently, we developed a framework for forecasting dengue incidence using an dynamical model of disease transmission coupled with observational data of dengue cases using data-assimilation methods. Here, we investigate the use of environmental data to drive the disease transmission model. We produce retrospective forecasts of the timing and severity of dengue outbreaks, and quantify forecast predictive accuracy.

  20. Evidence for the Inhibition of Dengue Virus Binding in the Presence of Silver Nanoparticles

    Science.gov (United States)

    2015-03-26

    with DENV are known to increase in severity from Dengue Fever to Dengue Hemorrhagic Fever or Dengue Shock Syndrome. Currently, no vaccines or...DENV is a member of the Flavivirus family, as is the yellow fever virus (the family’s prototype), West Nile, Japanese encephalitis virus, and many...perspective/2013/10/ researchers - identify-fifth-dengue-subtype. [20] C. Moore, “UTMB Galveston Researchers Discover First New Dengue Fever Serotype In 50

  1. Nine year trends of dengue virus infection in Mumbai, Western India

    OpenAIRE

    Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

    2017-01-01

    Introduction: Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, milit...

  2. Health System for Dengue Control : Early Case Detection and Focal Control

    OpenAIRE

    Umenai, Takusei; Nishigaki, Masaru; Osaka, Ken; Miura, Hiroko; Ishii, Katsumi

    1994-01-01

    "Aedes aegypti and dengue virus infection continue to spread in the tropical and subtropical world. Since there is no effective dengue vaccine, mosquito control and dengue patient treatment are the most important and practical way for dengue control. Many attempts have been made to control Aedes aegypti (adultcidal and larvicidal) to prevent dengue epidemic by large vertically-organized teams of workers. However, most of these methods have not been successful in the aspect of continuation of ...

  3. Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

    OpenAIRE

    Pires Neto,R.J.; Lima,D.M.; de Paula,S.O.; Lima,C.M.; Rocco,I.M.; Fonseca,B.A.L.

    2005-01-01

    Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appeara...

  4. Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil

    OpenAIRE

    Drumond, Betania Paiva; Fagundes, Luiz Gustavo da Silva; Rocha, Raissa Prado; Fumagalli, Marcilio Jorge; Araki, Carlos Shigueru; Colombo, Tatiana Elisa; Nogueira, Mauricio Lacerda; Castilho, Thiago Elias; Silveira, Nelson José Freitas da; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

    2016-01-01

    Abstract Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1–4) are antigenically and genetically...

  5. Factors related to severe dengue during an epidemic in Vitoria, State of Espirito Santo, Brazil, 2011

    OpenAIRE

    Vicente, Creuza Rachel; Lauar, Julia Castanheira; Santos, Bruna Silva; Cobe, Victor Marchesi; Cerutti Junior, Crispim

    2013-01-01

    Introduction The prognosis of dengue depends on early diagnosis and treatment, which can help prevent severe forms whose characteristics were evaluated here. Methods A cross-sectional study was conducted involving dengue cases in Vitória, State of Espírito Santo, Brazil, in 2011. Results Two health regions registered 56.3% of 371 cases of severe dengue. Of these cases, 21.3% presented with dengue hemorrhagic fever. There were associations between dengue hemorrhagic fever with yo...

  6. Studies on the surface antigenicity and susceptibility to antibody-dependent killing of developing schistosomula using sera from chronically infected mice and mice vaccinated with irradiated cercariae

    International Nuclear Information System (INIS)

    Bickle, Q.D.; Ford, M.J.

    1982-01-01

    Changes in the surface antigenicity and susceptibility to in vitro killing during development of schistosomula of Schistosoma mansoni were studied using serum from chronically infected mice (CIS) and from mice vaccinated with highly irradiated (20 krad) cercariae (VS). Binding of these sera was quantitated by counting the number of P388D 1 cells (a transformed, macrophage-like cell of mouse origin, bearing Fc receptors for IgG) binding to the parasite surface. Compared with schistosomula derived in vitro by mechanical transformation (MS), schistosomula recovered 3 hr after skin penetration in vitro (SS) showed a significant loss in surface binding of CIS. Schistosomula recovered 3 hr after skin penetration in vivo (SRS) showed even less binding, and this trend continued such that parasites recovered from the lungs 5 days after infection (LS) showed only minimal binding, and 10-day-old worms from the portal system showed no significant binding. In contrast, VS, which bound significantly less well to MS than CIS, showed enhanced binding to SS, and in the face of their declining antigenicity with respect to CIS, 3- to 24-hr SRS maintained this raised level of antigenicity. Although there appeared to be a decline in binding of VS thereafter, LS remained antigenic, still binding as many cells as MS did despite the fact that they also expressed host antigens detected usng antisera raised against mouse RBC. In spite of this persistence of VS binding up to the lung stage, resistance to eosinophil-mediated killing in vitro had developed by 48 hr post-infection, and LS were totally resistant to both eosinophil- and C-mediated killing

  7. Dengue in travellers: applicability of the 1975-1997 and the 2009 WHO classification system of dengue fever

    NARCIS (Netherlands)

    Wieten, Rosanne W.; Vlietstra, Wytze; Goorhuis, Abraham; van Vugt, Michèle; Hodiamont, Caspar J.; Leenstra, Tjalling; de Vries, Peter J.; Janssen, Saskia; van Thiel, Pieter P.; Stijnis, Kees; Grobusch, Martin P.

    2012-01-01

    Objectives The aim of this study was to assess the applicability and benefits of the new WHO dengue fever guidelines in clinical practice, for returning travellers. Methods We compared differences in specificity and sensitivity between the old and the new guidelines for diagnosing dengue and

  8. [Coexistence of acute appendicitis and dengue fever: A case report].

    Science.gov (United States)

    Osuna-Ramos, Juan Fidel; Silva-Gracia, Carlos; Maya-Vacio, Gerardo Joel; Romero-Utrilla, Alejandra; Ríos-Burgueño, Efrén Rafael; Velarde-Félix, Jesús Salvador

    2017-12-01

    Dengue is the most important human viral disease transmitted by mosquitoes. It can be asymptomatic or it can present in any of its 3clinical forms: Dengue fever, dengue haemorrhagic fever and dengue shock syndrome. However, some atypical manifestations have been reported in surgical emergencies caused by acute appendicitis in patients with dengue fever. We report the case of an 18-year-old Mexican male who presented to the emergency department of the General Hospital of Culiacan, Sinaloa, with symptoms of dengue fever, accompanied by crampy abdominal pain with positive Rovsing and Dunphy signs. Dengue infection was confirmed by a positive NS1 antigen test performed by enzyme-linked immunosorbent assay. An abdominal ultrasound revealed an appendicular process; as the abdominal pain in the right side kept increasing, an open appendectomy was performed. Abundant inflammatory liquid was observed during the surgery, and the pathology laboratory reported an oedematous appendix with fibrinopurulent plaques, which agreed with acute ulcerative appendicitis. The patient was discharged fully recovered without complications during the follow-up period. Acute abdominal pain can be caused in some cases by dengue infection. This can be confusing, which can lead to unnecessary surgical interventions, creating additional morbidities and costs for the patient. This unusual and coincident acute appendicitis with dengue highlights the importance of performing careful clinical studies for appropriate decision making, especially in dengue endemic regions during an outbreak of this disease. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Aspectos del dengue investigados en Santander

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    Ruth Martínez

    2004-03-01

    Full Text Available

    Entre 1998 y 2003 se registraron en Colombia 256,831 casos de dengue (22,834 de dengue hemorrágico DH de los cuales 41,325 (36% fueron en Santander (3,265 DH (1,2. En este período ocurrieron brotes en 1998 y 2001 observándose incremento de casos severos en el segundo (2. Por otro lado, existen inconvenientes con el diagnóstico que dificultan el manejo clínico oportuno y la vigilancia epidemiológica. Como consecuencia, los siguientes aspectos han sido investigados:

    1 Contribución de la circulación de los serotipos/genotipos al incremento del dengue hemorrágico, considerando que la entrada o emergencia de éstos se han asociado con epidemias (3. Entre 1998 y 2004 se hicieron 1,180 intentos de aislamiento viral en células C6/36 (4, detectándose los 4 serotipos. El DEN-2 se aisló todos los años con mayor frecuencia durante los brotes (43% y 40% de los cepas; el DEN-1 se detectó entre 1998 y 2001, siendo el prevalente en el primer brote (57%, pero el menos en el segundo (4%; el DEN-3 se detectó en el brote del 2001 con similar frecuencia al DEN-2 (36%, por primera vez en Colombia luego de 23 años ausente, y fue el prevalerte entre 2002-2004 (92% de los aislados, aunque en estos años no se reportó incremento del DH (2; el DEN-4 se aisló solo en el 2000 (27% y en el brote del 2001 (20%. El genotipo de cada serotipo se identificó por análisis de RSS-PCR (5,6. Se encontraron el subtipo A (ó III, C (ó I y B (ó II de los serotipos 2, 1 y 4, similares a los que están circulando en países de América y oriundos del Asia. Los DEN-3 fueron del subtipo C (ó III iguales al virus que entró en América en 1994 oriundo de Sri-Lanka, India. Los genotipos del 2 y 3 encontrados en Santander producen con mayor frecuencia DH (3,7.

    Evaluation of neurological complications using who warning signs for dengue disease severity

    International Nuclear Information System (INIS)

    Akmal, A.; Tauseef, A.; Akram, T.

    2015-01-01

    In 2009 a new classification of dengue was proposed by WHO Tropical Disease Research, which classifies dengue into dengue (D), dengue with warning signs (DW) and severe dengue (SD). This classification highlights the warning signs of dengue disease severity. Neurological complications are one of the most serious complications of dengue disease. This study was carried out to see association of neurological complications of dengue patients with WHO warning signs for dengue disease severity, and their outcome. Methods: It was a cross-sectional analytical study and included 180 diagnosed and registered cases of dengue hemorrhagic fever. The participants were subjected to a detailed clinical evaluation, laboratory assessment including blood counts, hematocrit, serology for dengue fever and sonography at 24 hours and 48 hours of their admission. Results: Twenty-six percent patients were suffering from neurological complications due to dengue. The warning signs for dengue disease severity like altered sensorium (85.5%, p=0.001), raised hematocrit (n=47, p=0.029), gall bladder wall thickening, pleural effusion and ascites on sonographic report (n=47, p=0.024), were strongly associated with the neurological complications. Conclusion: Our study reveals significant association of WHO warning signs for dengue disease severity with neurological complications of dengue disease. (author)

  10. Enhanced

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    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  11. Urbanização e ecologia do dengue Urbanization and dengue ecology

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    Pedro Luiz Tauil

    2001-01-01

    Full Text Available As mudanças demográficas ocorridas nos países subdesenvolvidos, a partir dos anos 60, geradas por intenso fluxo migratório rural-urbano, resultaram em crescimento desordenado das cidades, nas quais se destacam a carência de facilidades - em particular, de habitação e saneamento básico. Cerca de 20% da população das grandes e médias cidades estão vivendo em favelas, cortiços ou em áreas de invasão. Pela falta de abastecimento de água, há necessidade de armazená-la precariamente, tal como pela ausência de destino adequado do lixo ocorre a proliferação de criadouros potenciais do Aedes aegypti, principal mosquito vetor da dengue, ou seja, depósitos improvisados para água potável e recipientes em que a água é acumulada, constituídos principalmente por latas, plásticos e garrafas usadas. A indústria moderna, por outro lado, privilegia a produção de material descartável. O vírus do dengue tem sua propagação facilitada pela intensidade e freqüência dos meios de transporte, os quais favorecem também a disseminação dos vetores da doença. Estes são alguns dos fatores que tentam explicar o ressurgimento do dengue, a mais importante arbovirose no mundo atualmente e que acomete milhares de pessoas todos os anos.Demographic changes occurring in underdeveloped countries due to intense rural-urban migration since the 1960s have resulted in overcrowded cities with multiple deficiencies, particularly in housing and basic sanitation. Some 20% of the population in large and medium-sized cities live in slums or under similar conditions. Lack of regular water supply and public garbage collection foster the proliferation of potential breeding sites for Aedes aegypti (the main mosquito vector for dengue, including precarious reservoirs for potable water and disposable recipients which accumulate water, like used cans and plastic and glass bottles. Modern industries also produce large volumes of disposable materials. Propagation

  12. Molecular surveillance of dengue in Semarang, Indonesia revealed the circulation of an old genotype of dengue virus serotype-1.

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    Sukmal Fahri

    Full Text Available Dengue disease is currently a major health problem in Indonesia and affects all provinces in the country, including Semarang Municipality, Central Java province. While dengue is endemic in this region, only limited data on the disease epidemiology is available. To understand the dynamics of dengue in Semarang, we conducted clinical, virological, and demographical surveillance of dengue in Semarang and its surrounding regions in 2012. Dengue cases were detected in both urban and rural areas located in various geographical features, including the coastal and highland areas. During an eight months' study, a total of 120 febrile patients were recruited, of which 66 were serologically confirmed for dengue infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry and wet seasons. Majority of patients were under 10 years old. Most patients were diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and dengue fever. Serotyping was performed in 31 patients, and we observed the co-circulation of all four dengue virus (DENV serotypes. When the serotypes were correlated with the severity of the disease, no direct correlation was observed. Phylogenetic analysis of DENV based on Envelope gene sequence revealed the circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking finding was observed for DENV-1, in which we found the co-circulation of Genotype I with an old Genotype II. The Genotype II was represented by a virus strain that has a very slow mutation rate and is very closely related to the DENV strain from Thailand, isolated in 1964 and never reported in other countries in the last three decades. Moreover, this virus was discovered in a cool highland area with an elevation of 1,001 meters above the sea level. The discovery of this old DENV strain may suggest the silent circulation of old virus strains in Indonesia.

  13. Alterações hematológicas em pacientes com dengue Hematological abnormalities in patients with dengue

    Directory of Open Access Journals (Sweden)

    Éveny Cristine Luna de Oliveira

    2009-12-01

    Full Text Available Dengue é uma doença negligenciada de alta morbidade e mortalidade em crianças e adultos, ocorrendo principalmente em regiões tropicais e subtropicais. O objetivo desse trabalho foi avaliar as alterações hematológicas de pacientes com quadro clínico de dengue. Foram estudados 543 prontuários de atendimentos referentes à epidemia pelo vírus tipo 3, ocorrida no ano de 2007, em Campo Grande, Mato Grosso do Sul. Houve predomínio de casos de dengue clássico (90,2%, com quadro clínico leve sem complicações. As principais alterações hematológicas observadas foram a leucopenia (68,3%, plaquetopenia (66,5%, linfocitopenia (67,2% e presença de linfócitos atípicos (67%. A febre hemorrágica do dengue apresentou plaquetopenia mais prolongada e maior número de linfócitos atípicos, as demais alterações hematológicas apresentaram evolução diária semelhante às encontradas no dengue clássico. As alterações hematológicas observadas no dengue apresentaram-se de acordo com a evolução clínica e gravidade da doença.Dengue is a neglected disease with high morbidity and mortality among children and adults that occurs mainly in tropical and subtropical regions. The objective of this study was to evaluate hematological changes in patients with clinical manifestations of dengue. Medical records relating to 543 cases of dengue virus 3 that occurred during the 2007 epidemic in Campo Grande, Mato Grosso do Sul, were studied. Cases of classic dengue predominated (90.2%, with mild clinical manifestations lacking complications. The main hematological findings were leukopenia (68.3%, thrombocytopenia (66.5%, lymphocytopenia (67.2% and atypical lymphocytes (67%. In dengue hemorrhagic fever, thrombocytopenia was more prolonged and the number of atypical lymphocytes was higher, while the other hematological abnormalities presented daily evolution similar to those in classic dengue. The hematological changes observed in dengue present according

  14. Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data.

    Science.gov (United States)

    Zhang, Yingtao; Wang, Tao; Liu, Kangkang; Xia, Yao; Lu, Yi; Jing, Qinlong; Yang, Zhicong; Hu, Wenbiao; Lu, Jiahai

    2016-02-01

    Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information. We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC) curves and k-fold cross-validation. Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR) = 2.016, 95% Confidence Interval (CI): 1.845-2.203), controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC) for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967). The sensitivity and specificity

  15. Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data.

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    Yingtao Zhang

    2016-02-01

    Full Text Available Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information.We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC curves and k-fold cross-validation.Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR = 2.016, 95% Confidence Interval (CI: 1.845-2.203, controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967. The sensitivity and

  16. Mathematical analysis of dengue virus antibody dynamics

    Science.gov (United States)

    Perera, Sulanie; Perera, SSN

    2018-03-01

    Dengue is a mosquito borne viral disease causing over 390 million infections worldwide per annum. Even though information on how infection is controlled and eradicated from the body is lacking, antibodies are thought to play a major role in clearing the virus. In this paper, a non-linear conceptual dynamical model with humoral immune response and absorption effect has been proposed for primary dengue infection. We have included the absorption of pathogens into uninfected cells since this effect causes the virus density in the blood to decrease. The time delay that arises in the production of antibodies was accounted and is introduced through a continuous function. The basic reproduction number R0 is computed and a detailed stability analysis is done. Three equilibrium states, namely the infection free equilibrium, no immune equilibrium and the endemic equilibrium were identified and the existence and the stability conditions of these steady states were obtained. Numerical simulations proved the results that were obtained. By establishing the characteristic equation of the model at infection free equilibrium, it was observed that the infection free equilibrium is locally asymptotically stable if R0 1. Stability regions are identified for infection free equilibrium state with respect to the external variables and it is observed as the virus burst rate increases, the stability regions would decrease. These results implied that for higher virus burst rates, other conditions in the body must be strong enough to eliminate the disease completely from the host. The effect of time delay of antibody production on virus dynamics is discussed. It was seen that as the time delay in production of antibodies increases, the time for viral decline also increased. Also it was observed that the virus count goes to negligible levels within 7 - 14 days after the onset of symptoms as seen in dengue infections.

  17. Aedes albopictus and the reemergence of Dengue

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    Rezza Giovanni

    2012-01-01

    Full Text Available Abstract Dengue is a vector-borne disease that is estimated to affect millions of individuals each year in tropical and subtropical areas, and it is reemerging in areas that have been disease-free for relatively long periods of time. In this issue of the journal, Peng et al. report on a Dengue outbreak in a city in southern China that had been disease-free for more than two decades. The infection, which was due to serotype 1, was introduced by a traveler from South-east Asia and transmitted by Aedes albopictus, the Asian tiger mosquito. Compared to Aedes aegypti, which is the most important vector of Dengue, Ae albopictus is a less competent vector of arboviruses, and the epidemics it causes are milder. However, Ae albopictus is becoming an increasingly important vector because of its rapidly changing global distribution. In particular, the worldwide trade in second hand tires, which often contain water and are an ideal place for eggs and larvae, has been a key factor in the large-scale conquest of Ae albopictus, which easily adapts to new environments, even in a temperate climate. This expansion is creating new opportunities for viruses to circulate in new areas, becoming a common cause of epidemics in Ae aegypti-free countries, from Hawaii to Mauritius. The outbreak in China, like similar events, was mild and short-lived. Because epidemics due to Ae albopictus are milder, the replacement of Ae aegypti with the tiger mosquito could even result in public-health benefits. However, there is no solid evidence of this, and the milder course of the outbreak could be in part explained by the relatively short duration of the hot season in some affected areas. Since it is almost impossible to prevent Ae albopictus from being introduced in a country, mosquito-control measures at local level remain the most effective means of controlling arbovirus outbreaks.

  18. Mounting dengue awareness: A cost effective Strategy for prevention

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    Kajal Srivastava

    2015-12-01

    Full Text Available Background: Dengue is a serious illness which takes toll on human health every year. The best way to prevent it is by increasing awareness among common people. This study was conducted to assess the level of knowledge, attitudes and practices regarding dengue fever in people urban heath training centre in Pune, Maharashtra. Methods: A cross-sectional study was conducted among patients attending OPD of Urban heath training centre of department of community medicine, Pune situated in Ajmera, Pimpri, Pune. Through convenience sampling, a questionnaire was administered to patients after taking their informed consent. Results: A total of 100 patients were interviewed. Among knowledge 83% had heard about dengue and the most common source of information was TV & radio (72.3% Most of them were aware regarding mosquito bite being the mode of dengue transmission (80.7%. 22% were unaware regarding biting time of mosquito while 22% said night is the biting time of dengue mosquito. 62.7% were using coils for mosquito bite prevention followed by mosquito net (43.4% and spray (31.3%.. Conclusion: This study revealed that most of the study population is aware of dengue illness and increasing education level is having positive attitude on dengue illness.

  19. Mounting dengue awareness: A cost effective Strategy for prevention

    Directory of Open Access Journals (Sweden)

    Kajal Srivastava

    2015-12-01

    Full Text Available Background: Dengue is a serious illness which takes toll on human health every year. The best way to prevent it is by increasing awareness among common people. This study was conducted to assess the level of knowledge, attitudes and practices regarding dengue fever in people urban heath training centre in Pune, Maharashtra. Methods: A cross-sectional study was conducted among patients attending OPD of Urban heath training centre of department of community medicine, Pune situated in Ajmera, Pimpri, Pune. Through convenience sampling, a questionnaire was administered to patients after taking their informed consent. Results: A total of 100 patients were interviewed. Among knowledge 83% had heard about dengue and the most common source of information was TV & radio (72.3% Most of them were aware regarding mosquito bite being the mode of dengue transmission (80.7%. 22% were unaware regarding biting time of mosquito while 22% said night is the biting time of dengue mosquito. 62.7% were using coils for mosquito bite prevention followed by mosquito net (43.4% and spray (31.3%.. Conclusion: This study revealed that most of the study population is aware of dengue illness and increasing education level is having positive attitude on dengue illness.

  1. Clinical and virological characteristics of dengue in Surabaya, Indonesia.

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    Puspa Wardhani

    Full Text Available Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68% of them were children, and 47 (32% were adults. Dengue fever (DF and Dengue hemorrhagic fever (DHF were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53% samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%, followed by DENV-2 (8%, DENV-4 (8%, and DENV-3 (6%, while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

  2. Clinical and virological characteristics of dengue in Surabaya, Indonesia.

    Science.gov (United States)

    Wardhani, Puspa; Aryati, Aryati; Yohan, Benediktus; Trimarsanto, Hidayat; Setianingsih, Tri Y; Puspitasari, Dwiyanti; Arfijanto, Muhammad Vitanata; Bramantono, Bramantono; Suharto, Suharto; Sasmono, R Tedjo

    2017-01-01

    Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid ana